Day 3 :
- 3 Immune System Tumors
10 Immune checkpoint inhibitors
12 Combining Cancer Immunotherapies
14 Cancer Micro & Immuno Environment
17 Tumor biology
Location: Melbourne, Australia
Session Introduction
MarÃa del Rosario Dávalos Gamboa
University of San Simón, Bolivia
Title: Immune system, emotional problems and stress in kids and tenns with cancer of cochabamba, bolivia
Time : 11:15-11:40
Biography:
MarÃadel Rosario Dávalos Gamboa has completed her PhD at the Universidad Mayor Real and Pontifical San Francisco Xavier de Chuquisaca, Bolivia and Specialty in Clinical Biochemistry and Immunology at University of San Simón in Cochabamba, Bolivia. She was the Director of the Research Institute of the Faculty of Dentistry at the University of San Simón in Cochabamba, Bolivia. She is currently a Professor of the subject of Biochemistry of Faculty of Dentistry UMSS and is also majority shareholder of the industrial unit" Asociada Internacional de aceites y carbones SRL ACECAB" of Bolivia. She has published more than 10 articles in leading journals.
Abstract:
Introduction: In the Plurinational State of Bolivia is little known as influenced, of the status immunological, emotional problems and stress in cancer of children and adolescents. Objectives: The objective of this study was to determine the influence they had, the immune system, emotional problems and stress for the development of different types of cancer in children and adolescents in the region of Cochabamba, Bolivia. Methods: Cross-sectional study realized in January and February 2016, in children and adolescents who regularly attend in Hospital Manuel Ascencio Villarroel, with aged 2 months to 16 years of age (n=45) in the region of Cochabamba (Bolivia). Parents and or guardians of participants were surveyed. A descriptive analysis was performed. Results: They had two or more signs and symptoms (low immunity) that the immune system was weakened 86.67%. They were usually affected by influenza and viruses 51.11% had muscle pain and joint constant 44.44%, had watery eyes and nose running 35.55%, had persistent headache 40%, much tired and fatigued despite the rest 35.56%, sick regularly 31.11%, was delayed recovery of disease 28.88%, exhibited a fixed pattern of disease 28.88% and quarreled endlessly with the disease 24.44%. They had two or more warning signs, symptoms and physical changes in stress 79.26%. Especially, headache and stomach 53.33%, disturbance in food 51.11%, they felt anxious 48.89%, were too sensitive 46.67%, were tired 44.44%, had nightmares 37.77 %, they were distracted or thoughtful 33.33%, were concerned 31.11%, her hands sweat 22.22%. They had one or more emotional problems mismanaged, for loss, failure or trauma 60.0%. Often they felt: Distressed 40%, depressed or anxious 37.78%, exhausted 33.33%, felt fear or loneliness 22.22%, angry 20%, extreme anxiety 15.56% and nervous anguish 15.56%. Conclusions: This study found that for the development of cancer suffered by children and adolescents, they influenced both mismanaged emotional problems, as stress and especially the immune system weakened in them, as a result of psychosomatic disorders that exposed them to the disease.
Ben Tran
Eliza Hall Institute of Medical Research, Australia
Title: Immune profile and survival outcomes in stage 2 colon cancer
Time : 11:20-11:45
Biography:
Ben Tran is an medical oncologist who is heavily involved in drug development, molecular profiling and personalised medicine aiming to develop better treatments for cancer through laboratory research and clinical trials. His research focuses on matching people with the best treatment for their individual cancer. In particular, I am studying how the genome of cancer cells interacts with the body’s anti-tumour immune response. He is particularly interested in personalising cancer treatments, assessing potential new anti-cancer drugs through early phase clinical trials. He is also also pursuing studies of cancer immunotherapy. His medical practice focuses on urological and colorectal cancers, and He is currently conducting clinical trials using novel immunotherapeutic targeting these cancers.
Abstract:
Background Tumor associated immune response impacts outcomes in cancer. In colon cancer (CC), a good immune response, as represented by a dense lymphocytic infiltrate, is known to be associated with improved overall survival (OS). To date studies have used a subjective scoring system and OS benefits have been presumed to solely be the consequence of reduced cancer recurrence. The relationship with deficient mismatch repair (dMMR) status, a good prognostic marker that is typically associated with an immune infiltrate, remains unexplored. We examined an objectively determined Immune Profile (IP) and survival outcomes in stage 2 CC. Methods Stage 2 CC cases were identified from a hospital registry that prospectively records comprehensive point of care data, including recurrence free survival (RFS) and OS. MMR status was determined by immunohistochemistry. The density of CD3 and CD8 T-cells within each tumor was assessed by immunostaining and automated image analysis. A pattern recognition algorithm scored CD3 and CD8 density at the tumor core (TC) and invasive margin (IM). Raw scores for each region (CD3TC, CD3IM, CD8TC and CD8IM) were added and categorised as IP High or IP Low. Survival analyses used the Kaplan–Meier method and log-rank test. Results We included 463 subjects with stage II CC, median age 70.4 years, with median follow-up 57.7 months. 93 (16.5%) tumors were dMMR. 220 (47.5%) tumors were categorised as IP high. IP High was associated with improved survival outcomes compared to IP Low, including RFS (HR 0.25, p<0.001), post-recurrence survival (HR 0.20, p<0.001), cancer-specific survival (HR 0.08, p<0.001) and OS (HR 0.10, p<0.001). The improved RFS for IP high cases was independent of MMR status (dMMR: HR 0.10, p = 0.03; pMMR: HR 0.27, p<0.001). In patients without recurrence IP High was associated with reduced non-cancer deaths (HR 0.10, p<0.001). Conclusion Using an automated and objective measure, we have confirmed that immune infiltration is strongly associated with improved RFS and OS in stage II CC, independent of MMR status. We have also shown that a good immune response (IP High) is associated with post recurrence survival (where cancer recurs), and with reduced non-cancer mortality in patients that remain recurrence free.
Yoshihiro Komohara
Kumamoto University, Japan
Title: The significance of lymph node macrophages in the induction of anti-cancer immune response
Time : 11:45-12:10
Biography:
Yoshihiro Komohara has completed his PhD at the age of 29 years from Kumamoto University. He is a pathologist and now working at Kumamoto University as Associate Professor. He has studied tumor-associated macrophages for around 10 years and has published more than 20 papers related to CD163-positive tumor-associated macrophages. He has also focused on the relationship between cancer immunology and lymph node macrophages.
Abstract:
It is well known that many macrophages are distributed in lympho-reticular organs including spleen and lymph node (LN). Spleen and LNs are respectively involved in the filtration of lymph and blood flow, and immune responses are induced by activation of lymphocytes and natural killer cells which are dependent on antigen presenting cells (APCs) including dendritic cells and macrophages. CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggested that CD169+ macrophages in lymph nodes have tumor preventing properties; however, the role of these cells in the pathogenesis of human tumors has not been clarified. In order to determine the significance of CD169+ macrophages in cancer patients, we employed tissue samples from patients with malignant tumor including malignant melanoma and colorectal cancer and evaluated the relationships of this expression with overall survival and various clinicopathological factors. The high density of CD169+ cells was found to be significantly associated with a longer overall survival in the patients with malignant melanoma, colorectal cancer, and endometrial cancer. Positive correlations were noted between the density of CD169+ macrophages and the density of CD8+ cytotoxic T cells infiltrating tumor tissues. CD169+ macrophages in lymph node are suggested to be involved in T cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant tumors.
Nalini Kant Pati
Australian National University, Canberra, Australia
Title: Autoimmune disorders and Lymphoma
Time : 12:10-12:35
Biography:
Dr Nalini Pati is currently working as a consultant Adult and Paediatric Haematologist in Haematology Oncology in Canberra Hospital, Canberra and Clinical Senior Lecturer at Australian National University Medical School, Canberra, Australia. He has published more than 20 papers in reputed journals and has been serving as an editorial board member of few journal.
Abstract:
When autoimmunity began to emerge as a recognized disease process around 1950s, numerous studies linked several different autoimmune diseases with benign and malignant lympho-proliferative disorders in humans as well as animal models. Cuttner et al have investigated the relationship of prior autoimmune disease to the development of non-Hodgkin's lymphoma (NHL). Patients with NHL (n=278) seen during the 10 years period were compared with the controls, (n=317) seen at the same time. A comparison between these patient groups was performed based on various statistical analysis as well as logistic regression analysis to ascertain the risk of autoimmunity in NHL. 36 (13%) NHL patients had a prior autoimmune disease compared to 5% of controls (p=0.001). 69% of NHL patients with a prior autoimmune disease were female compared to 43% without a prior autoimmune disease and this was similar in control patients, 69% and 48%, respectively. 20% of all women with NHL had a history of autoimmune disease compared to 7% of women in the control group (p=0.001). 19 of the NHL patients with autoimmune disease (56%) received immunosuppressive treatment compared to 5 (38%) in the controls. Strength of association Existing clinical data on the autoimmunity-lymphoma association are rather meagre because many of the clinical studies have been anecdotal case collections rather than well studied prospective studies2. However, adequate studies establish strong associations between B cell lymphomas and Sjögren’s syndrome, autoimmune thyroiditis and autoimmune haemolytic anaemia. Apoptosis The role of defective apoptosis in the genesis of lymphoproliferation, autoimmunity and lymphoma was dramatically illustrated by the autoimmune lymphoproliferative syndrome (ALPS) of childhood. ALPS is the result of dominant heterozygous inheritance of a mutated (inactive) gene, (NIH), lymphoma occurred in 6 of 46 individuals, 13% of patients, usually long after the onset of ALPS at intervals from 6–48 years. Sustained antigen drive An example of such mechanism would be the chronic H. pylori infection that drives the host response, with T cell stimulation, ultimately generates an active lympho proliferating in B cell population. The ensuing MALT lymphoma will regress up to a certain point if H. pylori is eradicated. However, acquisition of particular chromosomal translocations among reactive B cells are lymphomogenic. Mutagenicity among B cells The third mechanism: B cell mutagenicity. Early B cell developmental events in the bone marrow operate to generate the B cell antigen receptor (BCR). Leading to further diversification of the BCR and developmwnt of lymphoproliferative disorder. Hodgkin’s disease: Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin’s lymphoma.6 Recent data also indicate that the risk of HL is increased following autoimmune diseases.7–9 Kristinsson et al, recently analyzed the association of a personal history of autoimmune conditions in 7,476 HL patients compared to 18,573 controls, and found several autoimmune conditions to be strongly associated with HL, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, and immune thrombocytopenic purpura (ITP). It was found that an overall 2.7-fold increased risk for all systemic autoimmune diseases combined.
Purwati
Universitas Airlangga, Indonesia
Title: The role of immunotherapy for stem cell cancer
Time : 13:25-13:50
Biography:
Purwati has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. 2015 be a chairman of stem cell research and development centre Universitas Airlangga Surabaya Indonesia. Have almost 50 publication in journals, papers, and seminar.
Abstract:
Aim: The role of immunotherapy for stem cell cancer. Method: Type of cancer are Carcinoma: Cancer of endo or ectoderm e.g., skin or epithelial lining of organs, Sarcomas: Cancer of mesoderm e.g., bone, Leukemias and Lymphomas: Cancers of hematopoietic cells. Molecular basis of cancer are dividing into three: The first is mutation was caused by radiation, chemicals and viruses; the second is up regulation of the proto oncogens and the third is down regulation of tumor suppressor genes. Cancer growth from cancer of stem cell with modality treatment of cancer was surgery, radiation, chemotherapy, Cryotherapy, radiofrequency, PBMCT, BMCT, until immunotherapy. Treatment modality was chosen depending on staging of cancer, but cancer of stem cell was known to resistance with conventional treatment, so for eliminated that the newest issue with immunotherapy. And also patients with metastasis staging of cancer usually also refracted with conventional treatment. So stem cell transplantation combination with immunotherapy will promise to give solution for that problem. Result: Haematopetic stem cell transplantation (HSCT) is a procedure to restoration bone marrow function as the result of giving cytotoxic drugs with or without whole body radiation. Source of stem cell from peripheral blood (PBMCs) or bone marrow or umbilical cord blood (UMCB) is autologus or allogenic. Conclusion: Stem cell combination with immunotherapy process was given separate or together, immunotherapy with NK cell or DCs autologous or allogenic. In vitro co culture between NK cell and leukemia cell, this cell could reduce the leukemia cell population, and also used in animal trial. Clinical trial on patient with solid tumor were treatment with immunotherapy with NK cell with the result of reducing of tumor size, with the reason because of NK cell have specific receptor as anti tumor, and also if given together with allogenic could prevent or decreasing rejection HSCT because of the unique properties of NK cell.
Roberta Mazzieri
The University of Queensland Diamantina Institute, Australia
Title: Tumor associated Tie2+ macrophages: Novel targets and effectors of anti-breast cancer therapies
Time : 13:50-14:15
Biography:
Roberta Mazzieri has obtained her PhD in Genetic Science from the University of Pavia, Italy and subsequently undertook one Post-doctoral position at the New York University, USA and two at the San Raffaele Scientific Institute in Milan, Italy. In 2012, she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications. The same year she was recruited by the University of Queensland, Brisbane to establish her own research group to continue her work on targeting pro-tumoral macrophages.
Abstract:
While advances in treatment and screening have greatly improved outcomes for most breast cancer patients, major unmet needs remain for treatment of patients with metastatic disease. Breast cancer has not benefitted to the same extent as other cancers from the recent introduction of immunotherapies due to poor inherent immunogenicity of breast tumors associated with a highly immunosuppressive microenvironment. New strategies are needed to overcome these limitations. We identified and characterized a subpopulation of pro-tumoral macrophages: The Tie2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogenic and immunosuppressive activities, both involving signaling through the ANG2/TIE2 pathway. Indeed we demonstrated that blocking the ANG2/TIE2 pathway disables the pro-angiogenic activity of TEMs resulting in inhibition of tumor angiogenesis, growth and metastasis in mouse models of breast carcinogenesis. We are now investigating whether the in vivo blockade of ANG2 is not only inhibiting the pro-angiogenic activity of TEMs, but also reverting their immunosuppressive activity, thus providing a strong rational for the development and testing of new combination therapies. Moreover, by exploiting the tumor homing ability of TEMs we turned them into an efficient vehicle for the tumor-targeted delivery of a potent immune-stimulatory molecule: Interferon-alpha (IFNα). We think that the multiple activities of type I IFNs in the complex network of cell interactions that lead to activation and deployment of immune responses may represent a valid strategy to promote and improve the outcome of cancer immunotherapy for the treatment of advanced breast cancer including lung and bone metastasis.
- 21 Immunotherapy Monitoring
18 Cancer biomarkers
23 Engineered T-cell Therapy
24 Novel Approches
Location: Melbourne, Australia
Session Introduction
Hsu-Shan Huang
Taipei Medical University, Taiwan
Title: Drug development for EGFR-TKI resistance in non-small cell lung cancer cells: novel dual inhibitor of EGFR and cMET
Time : 10:00-10:25
Biography:
Hsu-Shan Huang has completed his Dr. rer. nat. at the age of 34 years from Regensburg University, Germany and pharmaceutical studies from NDMC School of Pharmacy. He was the dean of School of Pharmacy and director of R&D, NDMC. He has published more than 95 SCI papers and 30 patents in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15% globally, accounting for more than 1.4 million deaths per year. Lung cancer is one of the most heavily mutated and genomically altered cancers. Despite the longer progression free survival of patients with TKI-treatment a high proportion eventually develop resistance. Resistance to targeted therapies is generally classified as either primary (i.e. intrinsic) or secondary (i.e. acquired). This approach has been variously termed “personalized cancer medicineâ€, “individualized cancer medicine†or “high precision cancer medicineâ€. Chemical synthesis led to further compound evaluations that revealed increased biochemical potency. The earliest efforts to utilize molecular profiling of tumors to guide more precise therapies for individual patients have met with remarkable success. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that NSC777201 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin-proteasomes. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKItargeting therapies.
Roberta Mazzieri
The University of Queensland Diamantina Institute, Australia
Title: Tumour associated Tie2+ macrophages: novel targets and effectors of anti-breast cancer therapies
Time : 10:25-10:50
Biography:
Dr Roberta Mazzieri obtained her PhD in Genetic Science from the University of Pavia (Italy) and subsequently undertook one post-doctoral position at the New York University (USA) and two at the San Raffaele Scientific Institute in Milan (Italy). In 2012 she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications. The same year she was recruited by the University of Queensland (Brisbane) to establish her own research group to continue her work on targeting pro-tumoural macrophages.
Abstract:
While advances in treatment and screening have greatly improved outcomes for most breast cancer patients, major unmet needs remain for treatment of patients with metastatic disease. Breast cancer has not benefitted to the same extent as other cancers from the recent introduction of immunotherapies due to poor inherent immunogenicity of breast tumours associated with a highly immunosuppressive microenvironment. New strategies are needed to overcome these limitations. We identified and characterized a subpopulation of pro-tumoural macrophages: the Tie2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogenic and immunosuppressive activities, both involving signalling through the ANG2/TIE2 pathway. Indeed we demonstrated that blocking the ANG2/TIE2 pathway disables the pro-angiogenic activity of TEMs resulting in inhibition of tumour angiogenesis, growth, and metastasis in mouse models of breast carcinogenesis. We are now investigating whether the in vivo blockade of ANG2 is not only inhibiting the pro-angiogenic activity of TEMs, but also reverting their immunosuppressive activity, thus providing a strong rational for the development and testing of new combination therapies. Moreover, by exploiting the tumor homing ability of TEMs we turned them into an efficient vehicle for the tumor-targeted delivery of a potent immune-stimulatory molecule: interferon-alphaï€ ï€¨IFNα. We think that the multiple activities of type I IFNs in the complex network of cell interactions that lead to activation and deployment of immune responses may represent a valid strategy to promote and improve the outcome of cancer immunotherapy for the treatment of advanced breast cancer including lung and bone metastasis.
George Kunuji
Bikbok Herbal Centre, Ghana
Title: Efficacy of Immune pressure on the progression of tumor and its escape
Time : 11:35-12:00
Biography:
Dr. George Kunuji attained his PhD from the University of Ghana, Legon and postdoctoral studies from University of Ghana Medical School. He is the director of Bikbok Herbal Centre, a reputable herbal organisation that is dispensing services across the country, Ghana and currently discovered herbal antidote to the treatment of cancer tumor. Moreover, he have been serving as the chairman of the health advocacy group of Asuboa Traditional Council and Nifahene(Nifa chief) of Asuboa Traditional Area.
Abstract:
Although cancers develop and being progress in immunocompetent hosts, immunological therapies for cancer have been proposed as an major alternative or complementary approaches to more standard therapy. It was initially thought to be that tumours were silent to the immune system, and that breaking immunological tolerance could result in immune-mediated tumour rejection. Attempts to develop combinatorial therapies by depleting suppressor cells or blocking suppressor pathways and at the same time actively inducing immune responses in vivo or adoptively transferring tumour-specific T cells have largely failed. Genomic testing is a rapidly developing area of medical science, there are currently only a few cancers where such testing is considered to be routine in the evaluation of possible treatment options. An overview reveals that the diagnoses of 3000 consecutively accessioned oral biopsies from the Oral Pathology. Depleted success has been achieved only against melanoma, using adoptive T-cell therapy, or prostate cancer, using a vaccine which improves patient survival but has no possible effective inhibitory effect on disease progression. This special issue is focused on understanding the escape mechanisms that malignant cells develop to destroy antitumor immune responses as well as strategies to overcome tumour escape. This drastic issue addresses many areas and one that can be talked of is the opposing function of the immune system in tumour inhibition and tumour progression. In that “cancer immune editing” describes the dual host-protecting and tumours-sculpting actions of the immune system that not only survey for, and elimininate, nascent malignant cells but also shape neoplastic disease through equilibrium and escape mechanisms. Many areas could further be elaborated on herbs and cancer tumour.
Biography:
Alex Agyekum has attained his PhD from the University of Ghana, Legon and Postdoctoral studies from University of Ghana Medical School. He is the Diagnostic Radiologist of Bikbok Herbal Centre, a reputable herbal organization that is dispensing services across the country, Ghana and currently discovered herbal antidote to the treatment of cancer tumor.
Abstract:
Diagnostic testing involves of specific disease tests and procedures to confirm the presence of disease and identify the correct tumour type, location, extent and stage. Our Herbal centre diagnostic team includes physicians across many medical specialties, including radiologists, pathologists and geneticists. However treatment is herbal base which is so effective and newly immerging in Ghana. A thorough and accurate cancer diagnosis is the eventually important first step in developing & Improving an individualized cancer treatment plan. A diagnostic plan test varies as follows: A preview of health history, Physical examination, Laboratory tests (blood, urine, etc.), Biopsy, Imaging tests (X-ray, PET/CT, MRI, ultrasound, etc.), Nuclear medicine scans (bone scans, etc.), Endoscopy and Genetic tests. Before treatment, we will accurately identified & locate tumours, stage the disease, and determine an appropriate combination of cancer treatments for you. Tumour molecular profiling helps us identify the right chemotherapy or targeted therapy Endoscopic ultrasound allows us to find and reach very small tumours without the risks of surgery. Genomic testing: BIKBOK Herbal Centre offers expanded genomic tumour assessment. This tool reveals the DNA alterations that are driving the growth of a cancer. All odontogenic neoplasm, neoplasm-like lesions (tumours), and true cysts of the oral tissues and jaws were listed. Of a total of 445 (1.11%) odontogenic tumours, 392 (0.98%) were lesions from patients in the usual local drawing area of the biopsy service; 53 were referred from distant centres. From the local population, odontomas were by far the most common tumour (51.53%) followed by ameloblastomas (13.52%) and peripheral odontogenic fibromas (8.93%). Locally, radicular (periapical) cysts were the most common odontogenic cyst (65.15%) followed by the dentigerous cyst (24.08%) and the odontogenic keratocyst (4.88%). The most common nonodontogenic cyst was the nasopalatine duct cyst that accounted for 73.43% of this subset of cysts. Surprisingly few studies of this type are available, especially for odontogenic tumours. The given data are not only Ghanaians but some visit our herbal centre from other west African countries in spite of the other centres having testing devices but our unique herbal treatment makes the difference.
Victoria Klepsch
Medical University Innsbruck, Austria
Title: Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T-cell signaling switch and emerging target in cancer immunotherapy
Time : 10:00-10:25
Biography:
Victoria Klepsch has received her PhD degree from the Medical University Innsbruck. She is a Postdoctoral Fellow at the Medical University Innsbruck in Gottfried Baier’s Lab. She has published 3 papers in well-reputed journals and has been working on NR2F6 and tumor immunology since 4 years continuing investigating in depth in this nuclear receptor NR2F6 in T-cell biology and cancer immunity.
Abstract:
Modulation of the immune system for the treatment of primary and metastatic tumors in cancer patients has been a goal for many decades. Very recently, blockade of immune checkpoints CTLA-4 and PD-1 has emerged as promising cancer immune therapies. Even though encouraging, there is an unmet medical need as still only a very limited number of patients respond to and are potentially cured by these therapies. In contrast to cell surface checkpoints, there are cancer therapeutic targets that are located inside the immune cells and are amenable to pharmacological modulation. Based on our published and unpublished findings that genetically NR2F6-deficient mice are able to immunologically reject otherwise lethal tumor burdens; we have identified and preclinically validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2, group F, member 6; alias Ear2 and COUP-TFIII) as a bona fide immune checkpoint. We could show that genetic ablation of NR2F6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, NR2F6-/- mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor re-challenge. This is paralleled by increased frequencies of both CD4+ and CD8+ T-cells and higher expression levels of interleukin-2 and interferon-ï§ at the tumor site. This defines NR2F6 as an intracellular and potentially also druggable immune checkpoint, where the presence of NR2F6 limits effector T-cell activation within the tumor microenvironment governing the amplitude of anti-cancer immunity, representing a promising avenue for development of alternative immune checkpoint inhibition treatment regimens.
Joanie Del Bano
Aix-Marseille University, France
Title: Bispecific antibodies in breast cancer immunotherapy
Time : 10:25-10:50
Biography:
Joanie Del Bano is a Pharmacist Resident and also pursuing PhD in Immuno-Oncology at the University of Aix-Marseille in the team "Therapeutic Antibodies and Immuno-targeting" led by Drs Daniel Baty and Patrick Chames. She is pursuing Pharmacy Residency Program at Marseille Public University Hospital. She is working on the development of bispecific antibodies for breast cancer immunotherapy.
Abstract:
Over the past 15 years, mounting evidence of the key contribution of NK cells in immunity against cancer has boosted the investigations into NK cell-based therapies. Among these strategies, antibody-based therapeutics is currently the fastest growing segment of the drug and biological market. However, tumor-targeting antibodies often have to face up an exhausted tumor environment responsible for their suboptimal effectiveness. Our objective is to manipulate NK cell functions and tumor targets using an original format of nanobody-based bispecific antibodies (bsFab) to revert the dampened immune response for treating breast cancer. Treatment and outcomes of HER2-amplified breast cancers have been revolutionized by the approval of trastuzumab. However, significant proportions of HER2 positive breast cancer are or become resistant due to de novo or acquired resistances. As well, triple negative breast cancers (TNBC) are intrinsically insensitive to most of the current targeted therapies such as hormonotherapy or trastuzumab. These cancers of poor prognosis remain a clinical challenge despite therapeutic innovations. We generate bispecific formats that display a unique, specific and high affinity for FcγRIII on NK cells and a moderate affinity for two tumor associated antigens: HER2 and mesothelin overexpressed in a large proportion of TNBC. NK antitumor effects driven by trastuzumab and bsFabs, alone or in combination, were investigated on different 2D and 3D breast cancer models. Our data underline the potential of these bsFabs to enlarge the number of patients eligible for breast cancer immunotherapy and prompt to consider combination strategies.
Shimae Nafarzadeh
Babol University of Medical Sciences, Iran
Title: Role of mast cells in oral squamous cell carcinoma
Time : 11:10-11:35
Biography:
Shimae Nafarzadeh has completed her DDS in Dentistry in 2004 and Specialty in Oral and Maxillofacial Pathology in 2007 from Shahid Beheshti University of Medical Sciences, Tehran, Iran. She has been working as a University Professor in the Oral and Maxillofacial Pathology Department of Babol Dentistry School since 2007 and recently became the Dean of the Department.
Abstract:
There are controversial findings about the role of mast cells in tumor progression. Some researchers believe mast cells play role in immunologic host defense, while some believe mast cells role in tumor progression. We conducted a systematic review article by surfing the PubMed and Scopus data bases and found 14 articles from 2000 to 2015. Mast cells are considered to have diverse biological functions such as phagocytosis, antigen processing, release of cytokines and preformed or newly formed mediators, hemostasis and inflammation. Mast cells also can affect angiogenesis by producing factors such as Heparin, Histamine, VEGF, Chymase, b-FGF, TGF-beta which certainly influence tumor growth. Role of mast cells as MMP activators has been identified. MMP-9 plays an important role in tumor metastasis and invasion through affecting angiogenesis and cleaving basement membrane. Considering poor prognosis of OSCC in spite of new therapeutic methods, it seems that mast cells could be good targets for future research and finding ways for their disactivation and suppression of their secretions is of great value for producing future anticancer drugs.
- Poster Presentation
Location: Melbourne, Australia
Session Introduction
Hussein A. Kaoud
Cairo University, Giza-Egypt
Title: Molecular Tumor Markers: Diagnosis and Therapy
Time : 14:15-15:35
Biography:
Hussein Abd Elhay Kaoud is a full Professor at Cairo University, Egypt. He has published more than 190 articles and scientific books and patents. He is a Member of several Egyptian and international societies. He is the Editor and Reviewer of many international journals and received many awards.
Abstract:
Molecular tumor markers can be produced directly by tumor or non tumor cells as a response to the presence of a tumor. Most tumor markers are tumor antigens but not all tumor antigens can be used as tumor markers. Molecular markers are diagnostic, prognostic or predictive. The article discussed the molecular tumor markers; significance of each markers and its role in diagnosis, prognosis and prediction of tumor and tests used. It is used to distinguish tumor from normal tissue or to detect the presence of a tumor on the basis of measurements in the blood or secretions. And it is currently being put new molecular markers with an increased understanding of the molecular environment of the cell tumor and other disease cells. It can produce tumor markers directly from the tumor or by non-cancer cells in response to the presence of a tumor. Most tumor markers are tumor antigens but not all tumor antigens can be used as tumor markers. Concerning drug evaluation and check effects of drug treatment on the tumor, biomarkers perhaps can determine the appropriate dose in the early stages of a new antidepressant medication for cancer clinical development. Biomarkers and prognostic expects the natural course of cancer and excellence as a result of the tumor. They also help determine who to treat, how aggressively to treat and which candidates are likely to respond to a particular drug and the dose is most effective. Theranostic, use a combination of diagnosis and therapy sessions and can be different perception. Imaging can be used to track drug delivery within the body. However, imaging can also be used to stimulate drug releasing from the outside by external influences. These external influences to be laser light, temperature or ultrasound, for example. In the forefront, smart probes represent new innovative concepts for clinical application. Nanoparticles can be used to make selective surfaces for molecular interactions target. For example the population H biomarker present in the blood will be characterized fully, pads harvesting nano-particle has a great potential to improve the detection of the disease at an early stage and more treatable.
Afaf Ibrahim
Alexandria University, Egypt
Title: Determination of a cut-off point for Prostatic Specific Antigen (PSA) to avoid unjustified biopsy among asymptomatic Egyptians
Time : 14:15-15:35
Biography:
Afaf Gaber Ibrahim Salama Elhanash is currently a Professor of Public Health, Social and Preventive Medicine. Community medicine and Public Health Department, Alexandria Faculty of Medicine. Egypt. She is also a Head of Evidence based clinical practice guidelines center affiliated to Healthcare Quality Directorate of Alexandria university hospitals. (Founded Nov. 2008, Member of Guidelines International Network (G-I-N Since May 2009 ), Visiting professor in Arabic Bierut University in Lebanon in 2001, WHO Short term consultant: Participated as an international supervisor in conducting Retrospective Crude Mortality survey conducted in Greater Darfur Region, Sudan in May-June 2005 & Visiting Professor at Arab Academy for Science ,Technology and maritime transport as course instructor of Best Practice Guidelines course for Master of health care management. She has published many articles in reputed journals.
Abstract:
Introduction & Objectives: In Egypt, there is no national screening program for prostate cancer. The Urology Department in Alexandria University established a screening program for prostate cancer among men aged more than 55 years in January 2012. The aim of the present study was to determine a PSA cut-off point for performing Transrectal Ultrasonography (TRUS) guided biopsy among asymptomatic men. Material & Methods: This study included 1207 men aged more than 55 year of age who were attending Urology Department, Alexandria University for non prostatic symptoms and accepted to be screened. Digital Rectal Examination (DRE) and PSA level measurement were performed for all included subjects. Transrectal ultrasonography (TRUS) guided biopsy was done for those who found to have PSA>4 ng/ml and or suspicious DRE. Results: A minority of screened subjects (13%) had PSA of more than 4 ng/ml. Transrectal ultrasonography (TRUS) guided biopsy was performed for 157 subjects who had PSA>4 ng/ml and or suspicious DRE findings. One patient with a PSA>4 ng/ml who had suspicious DRE finding proved by TRUS biopsy to have prostate cancer giving PPV=100. Among those who have PSA level of 4.1-10, PPV is 54 among those with suspicious DRE findings as compared to 0 among those with non suspicious DRE. A higher PPV is observed for those who had PSA level of 10.1-20 and >20 with suspicious DRE findings (77 and 100 respectively). The mean serum total PSA was 77 and 0.6 ng/ ml for patients with and without prostatic cancer respectively (p=0.0001). The yield of cancer prostate among all screened patients was 103/1207=8% and 103/157=65% among those with PSA>4 ng/ml and were biopsied. Considering all the patients who had biopsy based on PSA and or DRE, ROC curve could derive a cut-off value of 10.05 ng/ml with a sensitivity of 92 percent and a specificity of 92.6 percent (area under curve, AUC 0.973±0.012, 95% CI (.950-0.997 P<0.000). The likelihood ratio is sensitivity/1-specificity=12.43. Conclusions: In a country of relatively low prevalence of prostate cancer like Egypt, a cut-off point of PSA in combination with DRE for doing TRUS biopsy could be 10.05 ng per ml among asymptomatic men of more than 55 years of age with a likelihood ratio of 12.43
Takehiko Okamura
Anjo Kosei Hospital, Aichi Prefecture 446-8602, Japan
Title: Neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for long-term interleukin-2 (IL-2) use in metastatic renal cell carcinoma
Time : 14:15-15:35
Biography:
Takehiko Okamura has completed his Doctorate in Medical Genetics in 1988. From 1989 to 1991, he was a Research Fellow at the Department of Pathology and Microbiology, University of Nebraska Medical Center, under a famous researcher of bladder carcinogenesis, Dr. Samuel M. Cohen. He studied bladder carcinogenesis and molecular biology. Over the past 30 years, he has continued to conduct clinical and translational research, mainly on BCG immunotherapy for non-muscle invasive bladder cancer. He has published more than 25 papers as a first author.
Abstract:
Because of the introduction of molecular targeted drugs, the treatment of renal cell carcinoma has greatly evolved and patient prognosis has remarkably improved. Molecular targeted drugs are now used for patient therapies instead of cytokines alone. However, treatment of this disease is affected by the drug administration method or when the drug is changed; although sequential therapy with molecular targeted drugs has attracted attention, a clear parameter to judge its effectiveness does not exist. On the other hand, the effectiveness of immunotherapy, which set the transverse axis of the T-cell, can be evaluated by the appearance of anti-PD-1 antibody. In this study, we retrospectively examined three cases of metastatic renal cell carcinoma, which were treated with the long-term use of interleukin-2 (IL-2), with regard to the usefulness of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor. All three cases were males; 2 were in their 50s and the other was in his 60s. The cases were administered IL-2 for 2.5, 3 and 7 years, respectively. For all cases, interferon-alpha was administered before IL-2 and after IL-2 administration, all cases were switched to molecular targeted drugs and each case could continue cancer treatment more than 3 years after starting IL-2. And finally, NLR have not raised, less than 2.7 during IL-2 treatment. The results suggested that NLR might serve as a useful marker for therapies when determining prognosis. Further studies including a prospective study in Japan and comparison with large-scale databases will be necessary.
- Workshop / Special Session
Location: Melbourne, Australia
Session Introduction
Weidong Han
Professor Chinese PLA General Hospital China
Title: Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with sorafenib refractory hepatocellular carcinoma (HCC) and other solid tumors
Time : 11:50-12:50
Biography:
Weidong Han has obtained his PhD degree in Clinical Hematology from Chinese PLA Postgraduate Medical School in 2001 and worked in Department of Molecule & Immunology of Chinese PLA General Hospital. In 2003, he did Postdoctoral work at the University College London. In 2006, he was promoted to Professor of Molecular and Cellular Biology. Presently, he is the Director of Department of Molecular and Cellular Biology, Director of Clinical Translational Ward, the General Hospital of PLA. Since 2001, he focused on mechanism research involved in cancer treatment resistance and clinical translation of cell therapy. He has published over 80 articles.
Abstract:
CD133 is well documented to be expressed by tumor initiating cells and epithelial progenitor cells which were proposed to have predominant roles for tumor recurrence and pre-metastatic niche formation, respectively. Thus, targeting CD133 might help eradicate the primary tumors and even prevent tumor metastasis. Herein, CD133-directed chimeric antigen receptor modified T-cells (CART-133) were prepared and their specific targeting activity was verified. Results from hematopoietic colony forming assays suggested that CART-133 cells may pose no irreversible myelosuppression. Eight patients with advanced and sorafenib refractory HCC were enrolled on phase-I trial. They were assigned into 3 dose-escalated cohorts and were treated by repeated CART-133 monotherapy once 4-8 weeks. All patients had tolerable febrile syndromes during cell infusions. Rapid ascites growth occurred in 1 patient during infusion and was resolved by the use of diuretic. One patient developed transiently drastic decline of hemoglobin and platelets and Grade 3 direct hyperbilirubinemia within 2 weeks. Reverse correlation between CD133+ cells in PB and CAR copy number in cohort 2 and 3 revealed an effective biological activity of CART-133 and its rational expansion dose. 1 of 3 cases in cohort 1 aggressively progressed after cell therapy and became stable after transferred to cohort 2. Seven cases maintained stable disease so far, however, 2 patients died of upper gastrointestinal massive hemorrhage >9 weeks after infusion. Based on these, 7 additional patients with other metastatic solid tumors were enrolled into phase-II trial using the expansion dose, the response of which is under evaluation.
Hsu-Shan Huang
Taipei Medical University, Taiwan
Title: Drug development for EGFR-TKI resistance in non-small cell lung cancer cells: novel dual inhibitor of EGFR and cMET
Time : 13:50-14:50
Biography:
Hsu-Shan Huang has completed his Dr. rer. nat. at the age of 34 years from Regensburg University, Germany and pharmaceutical studies from NDMC School of Pharmacy. He was the dean of School of Pharmacy and director of R&D, NDMC. He has published more than 95 SCI papers and 30 patents in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15% globally, accounting for more than 1.4 million deaths per year. Lung cancer is one of the most heavily mutated and genomically altered cancers. Despite the longer progression free survival of patients with TKI-treatment a high proportion eventually develop resistance. Resistance to targeted therapies is generally classified as either primary (i.e. intrinsic) or secondary (i.e. acquired). This approach has been variously termed “personalized cancer medicine”, “individualized cancer medicine” or “high precision cancer medicine”. Chemical synthesis led to further compound evaluations that revealed increased biochemical potency. The earliest efforts to utilize molecular profiling of tumors to guide more precise therapies for individual patients have met with remarkable success. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that NSC777201 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin-proteasomes. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKItargeting therapies.
- 4 Immunotherapy-Tumors
9 Cancer Immunology & Immunotherapy
11 Cancer Research
13 Tumor immunotherapy research
14 Tumor markers and drug targetting
Location: Melbourne, Australia
Session Introduction
Weidong Han
Professor Chinese PLA General Hospital China
Title: Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with sorafenib refractory hepatocellular carcinoma (HCC) and other solid tumors
Time : 11:50-12:50
Biography:
Weidong Han has obtained his PhD degree in Clinical Hematology from Chinese PLA Postgraduate Medical School in 2001 and worked in Department of Molecule & Immunology of Chinese PLA General Hospital. In 2003, he did Postdoctoral work at the University College London. In 2006, he was promoted to Professor of Molecular and Cellular Biology. Presently, he is the Director of Department of Molecular and Cellular Biology, Director of Clinical Translational Ward, the General Hospital of PLA. Since 2001, he focused on mechanism research involved in cancer treatment resistance and clinical translation of cell therapy. He has published over 80 articles.
Abstract:
CD133 is well documented to be expressed by tumor initiating cells and epithelial progenitor cells which were proposed to have predominant roles for tumor recurrence and pre-metastatic niche formation, respectively. Thus, targeting CD133 might help eradicate the primary tumors and even prevent tumor metastasis. Herein, CD133-directed chimeric antigen receptor modified T-cells (CART-133) were prepared and their specific targeting activity was verified. Results from hematopoietic colony forming assays suggested that CART-133 cells may pose no irreversible myelosuppression. Eight patients with advanced and sorafenib refractory HCC were enrolled on phase-I trial. They were assigned into 3 dose-escalated cohorts and were treated by repeated CART-133 monotherapy once 4-8 weeks. All patients had tolerable febrile syndromes during cell infusions. Rapid ascites growth occurred in 1 patient during infusion and was resolved by the use of diuretic. One patient developed transiently drastic decline of hemoglobin and platelets and Grade 3 direct hyperbilirubinemia within 2 weeks. Reverse correlation between CD133+ cells in PB and CAR copy number in cohort 2 and 3 revealed an effective biological activity of CART-133 and its rational expansion dose. 1 of 3 cases in cohort 1 aggressively progressed after cell therapy and became stable after transferred to cohort 2. Seven cases maintained stable disease so far, however, 2 patients died of upper gastrointestinal massive hemorrhage >9 weeks after infusion. Based on these, 7 additional patients with other metastatic solid tumors were enrolled into phase-II trial using the expansion dose, the response of which is under evaluation.
Hsu-Shan Huang
Taipei Medical University, Taiwan
Title: Drug development for EGFR-TKI resistance in non-small cell lung cancer cells: novel dual inhibitor of EGFR and cMET
Time : 13:45-14:30
Biography:
Hsu-Shan Huang has completed his Dr. rer. nat. at the age of 34 years from Regensburg University, Germany and pharmaceutical studies from NDMC School of Pharmacy. He was the dean of School of Pharmacy and director of R&D, NDMC. He has published more than 95 SCI papers and 30 patents in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15% globally, accounting for more than 1.4 million deaths per year. Lung cancer is one of the most heavily mutated and genomically altered cancers. Despite the longer progression free survival of patients with TKI-treatment a high proportion eventually develop resistance. Resistance to targeted therapies is generally classified as either primary (i.e. intrinsic) or secondary (i.e. acquired). This approach has been variously termed “personalized cancer medicineâ€, “individualized cancer medicine†or “high precision cancer medicineâ€. Chemical synthesis led to further compound evaluations that revealed increased biochemical potency. The earliest efforts to utilize molecular profiling of tumors to guide more precise therapies for individual patients have met with remarkable success. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that NSC777201 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin-proteasomes. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKItargeting therapies.
Maria Marcela Barrio
Centro de Investigaciones Oncológicas Fundación Cáncer, Argentina
Title: CSF-470 vaccine plus BCG plus rhGM-CSF show superiority vs. IFN-α2b in high risk cutaneous melanoma patients stages IIB, IIC and III: Interim results of the phase II part of phase II/III CASVAC0401 study
Time : 14:50-15:15
Biography:
Maria Marcela Barrio was graduated in 1991 as a Biologist at the University of Buenos Aires and obtained her PhD working on monoclonal antibodies at the Fundación Instituto Leloir. She became a Member of The National Scientific and Technical Research Council (CONICET) in 2007. She has been working in the cancer immunology as part of Dr. Mordoh´s team since 1984. Presently she is Sub-Director of the Centro de Investigaciones Oncológicas Fundación Cáncer. She has published more than 40 scientific papers about her specialty and she is working in translational research for the development of therapeutic vaccines for cutaneous melanoma.
Abstract:
Adjuvant treatment of high-risk cutaneous melanoma (CM) patients is still an unsolved issue. The CSF-470 therapeutic vaccine, a mixture of lethally irradiated allogeneic CM cell lines, combined with BCG and rhGM-CSF as adjuvants is currently tested in post-surgical adjuvancy against medium-dose IFN-α2b in stage IIB-III CM patients (CASVAC-0401 phase II-III study). Here we present the results of the phase II part of the study. Patients in the vaccine arm (n=20) received 1.6×107 CSF-470 melanoma irradiated cells i.d. plus 106 cfu BCG and 400 μg rhGM-CSF fractionated in 4 consecutive days were i.d. injected at the vaccination site, during 2 years (13 vaccinations in total). IFN-α2b patients (n=11) received 10 MU/day/5 days a week for 4 weeks; then 5 MU/day thrice weekly for 23 months (m). CSF-470 was well tolerated. The main toxicity was grade 2 reaction at the vaccination site (20/20); 3/20 patients presented grade 3 allergic reactions, easily handled with anti-histamines and corticosteroids; the rest of the AE were grade 1. IFN-α2b patients presented grade 2-3 hematologic (7/11), hepatic (2/11) and cardiac (1/11) toxicity, 9/11 patients developed AE that forced treatment discontinuation. QOL was significantly superior in CSF-470 arm vs. IFN-α2b arm. With a maximum follow-up of 72 m (Mean: 28 m) a significant benefit in the distant metastasis-free (DMF) survival for CSF-470 was observed (p=0.028). No significant differences in OS were yet observed. DTH reaction after the 7th vaccine was higher in distant metastasis-free patients than in progressing patients. Immune monitoring at 6 months showed an increase in NK cells (p=0.009) and a slight decrease in Tregs (p=0.021) in vaccinated patients; conversely IFN-α2b patients showed a significant decrease in total CD3+, CD4+ and CD8+T cells; serum Abs reactive with vaccine CM cells increased in all vaccinated patients (p<0.0001), but not in IFN-α2b patients. CSF-470 vaccine +BCG +GM-CSF superiority vs. IFN-α2b for adjuvant treatment of high-risk CM observed so far encourage continuation of the phase III part of CASVAC0401 study.
MarÃa del Rosario Dávalos Gamboa
University of San Simón, Bolivia
Title: Immune system, emotional problems and stress in kids and tenns with cancer of cochabamba, bolivia
Time : 15:15-15:40
Biography:
Maríadel Rosario Dávalos Gamboa has completed her PhD at the Universidad Mayor Real and Pontifical San Francisco Xavier de Chuquisaca, Bolivia and Specialty in Clinical Biochemistry and Immunology at University of San Simón in Cochabamba, Bolivia. She was the Director of the Research Institute of the Faculty of Dentistry at the University of San Simón in Cochabamba, Bolivia. She is currently a Professor of the subject of Biochemistry of Faculty of Dentistry UMSS and is also majority shareholder of the industrial unit" Asociada Internacional de aceites y carbones SRL ACECAB" of Bolivia. She has published more than 10 articles in leading journals.
Abstract:
Introduction: In the Plurinational State of Bolivia is little known as influenced, of the status immunological, emotional problems and stress in cancer of children and adolescents. Objectives: The objective of this study was to determine the influence they had, the immune system, emotional problems and stress for the development of different types of cancer in children and adolescents in the region of Cochabamba, Bolivia. Methods: Cross-sectional study realized in January and February 2016, in children and adolescents who regularly attend in Hospital Manuel Ascencio Villarroel, with aged 2 months to 16 years of age (n=45) in the region of Cochabamba (Bolivia). Parents and or guardians of participants were surveyed. A descriptive analysis was performed. Results: They had two or more signs and symptoms (low immunity) that the immune system was weakened 86.67%. They were usually affected by influenza and viruses 51.11% had muscle pain and joint constant 44.44%, had watery eyes and nose running 35.55%, had persistent headache 40%, much tired and fatigued despite the rest 35.56%, sick regularly 31.11%, was delayed recovery of disease 28.88%, exhibited a fixed pattern of disease 28.88% and quarreled endlessly with the disease 24.44%. They had two or more warning signs, symptoms and physical changes in stress 79.26%. Especially, headache and stomach 53.33%, disturbance in food 51.11%, they felt anxious 48.89%, were too sensitive 46.67%, were tired 44.44%, had nightmares 37.77 %, they were distracted or thoughtful 33.33%, were concerned 31.11%, her hands sweat 22.22%. They had one or more emotional problems mismanaged, for loss, failure or trauma 60.0%. Often they felt: Distressed 40%, depressed or anxious 37.78%, exhausted 33.33%, felt fear or loneliness 22.22%, angry 20%, extreme anxiety 15.56% and nervous anguish 15.56%. Conclusions: This study found that for the development of cancer suffered by children and adolescents, they influenced both mismanaged emotional problems, as stress and especially the immune system weakened in them, as a result of psychosomatic disorders that exposed them to the disease.
William Jia
University of British Columbia, ViroGin Biotech Ltd, Canada
Title: Oncolytic HSV-1 with enhancement of both oncolysis and safety
Time : 16:00-16:25
Biography:
William Jia has completed his PhD in 1991 at University of British Columbia (UBC) in Molecular Neurosciences. He has been an Associate Professor since 1999 at UBC and an Associate Scientist of BC Cancer Research Centre. He has been a Conjunct Professor of Fudan University, Shanghai Institute of Pharmaceutical Industry and the VP (research) for Shanghai Innovative Research Centre of Traditional Chinese Medicine (SIRC-TCM). He was the first in Canada and the first few scientists in the world using human Herpes simplex virus to treat cancer, which pioneered the field of oncolytic virotherapy for cancer treatment. He has developed one gene therapy drug for malignant gliomas has completed a phase I clinical trial in China. His most recent contribution is to raise the concept of transcription and translation dual regulated (TTDR) oncolytic viruses for cancer treatment. In the past years, he has received many awards and research funds. Since 1997, he has been a Scholar of Canadian Institute of Health Research. He has also received Petro Canada Young Inventors Award in 2007.
Abstract:
Oncolytic virotherapy has attracted increasing attention due to recent approval of T-VEC by FDA. Although anti-tumor immune response is a critical mechanism for oncolytic virotherapy, strong oncolytic viral activity for extensive cell lysis and virus dissemination inside of tumor also play a pivotal role for better therapeutic efficacy. However, it has always been a challenge to create an oncolytic virus that is highly oncolytic but also tumor specific for safety. In past years, we have been developing strategies that allow not only to enhance the safety but also to increase oncolytic activity at the same time. Those strategies include transcriptional and translational dual regulation on essential viral gene expression, overcoming macrophage/microglia barriers for better viral spreading in the tumor mass and enhancing virus oncolytic activity by inhibiting both anti-viral and oncogene cellular signals by a small molecule. We would present examples of those strategies and show their effects in animal tumor models.
Purwati
Universitas Airlangga, Indonesia
Title: The role of immunotherapy for stem cell cancer
Time : 16:00-16:25
Biography:
Purwati has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. 2015 be a chairman of stem cell research and development centre Universitas Airlangga Surabaya Indonesia. Have almost 50 publication in journals, papers, and seminar.
Abstract:
Aim: The role of immunotherapy for stem cell cancer. Method: Type of cancer are Carcinoma: Cancer of endo or ectoderm e.g., skin or epithelial lining of organs, Sarcomas: Cancer of mesoderm e.g., bone, Leukemias and Lymphomas: Cancers of hematopoietic cells. Molecular basis of cancer are dividing into three: The first is mutation was caused by radiation, chemicals and viruses; the second is up regulation of the proto oncogens and the third is down regulation of tumor suppressor genes. Cancer growth from cancer of stem cell with modality treatment of cancer was surgery, radiation, chemotherapy, Cryotherapy, radiofrequency, PBMCT, BMCT, until immunotherapy. Treatment modality was chosen depending on staging of cancer, but cancer of stem cell was known to resistance with conventional treatment, so for eliminated that the newest issue with immunotherapy. And also patients with metastasis staging of cancer usually also refracted with conventional treatment. So stem cell transplantation combination with immunotherapy will promise to give solution for that problem. Result: Haematopetic stem cell transplantation (HSCT) is a procedure to restoration bone marrow function as the result of giving cytotoxic drugs with or without whole body radiation. Source of stem cell from peripheral blood (PBMCs) or bone marrow or umbilical cord blood (UMCB) is autologus or allogenic. Conclusion: Stem cell combination with immunotherapy process was given separate or together, immunotherapy with NK cell or DCs autologous or allogenic. In vitro co culture between NK cell and leukemia cell, this cell could reduce the leukemia cell population, and also used in animal trial. Clinical trial on patient with solid tumor were treatment with immunotherapy with NK cell with the result of reducing of tumor size, with the reason because of NK cell have specific receptor as anti tumor, and also if given together with allogenic could prevent or decreasing rejection HSCT because of the unique properties of NK cell.
Qiaofei Liu
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, China
Title: Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection
Time : 16:25-16:50
Biography:
Qiaofei Liu has completed his MD at the age of 24 years from School of Medicine, Nankai University. He is now a attending surgeon of general surgery department in Peking Union Medical School College Hospital.His main interests are precise surgery and integrated treatments for pancreatic cancer. He has published more than 10 papers in reputed journals and has been serving as an editorial board member of 3 international journals.
Abstract:
Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86% of tumor tissue samples compared with 69% of peritumoral tissue samples (P = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade (P = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis (P = 0.01) in multivariate analysis. We further found that intratumoral M2 polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2 polarized TAMs probably induce IgG4-positive plasma cells.
George Kunudji
Asuboa traditional council hearth advocacy group, Ghana
Title: Cancer/testis antigens: an expanding family of targets for cancer immunotherapy
Time : 15:35-16:00
Biography:
george kunudji has completed his PhD at the age of 25 years from Andhra University and postdoctoral studies from Stanford University School of Medicine. He is the director of a premier Bio-Soft service organization. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of repute
Abstract:
Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. In some cases, CT antigens are also expressed in ovary and in trophoblast. In malignancy, this gene regulation is disrupted, resulting in CT antigen expression in a proportion of tumors of various types. Since their initial identification by T-cell epitope cloning, the list of CT antigens has been greatly expanded through serological expression cloning (SEREX) and differential mRNA expression analysis, and approximately 20 CT antigens or antigen families have been identified to date. Characteristics commonly shared by CT antigens, aside from the highly tissue-restricted expression profile, include existence as multigene families, frequent mapping to chromosome X, heterogeneous protein expression in cancer, likely correlation with tumor progression, induction of expression by hypomethylation and/or histone acetylation, and immunogenicity in cancer patients. Spontaneous humoral and cell-mediated immune responses have been demonstrated against several CT antigens, including NY-ESO-1, MAGE-A, and SSX antigens. Since CT antigens are immunogenic and highly restricted to tumors, their discovery has led directly to the development of antigen-specific cancer vaccines, and clinical trials with MAGE-A and NY-ESO-1 are in progress.