2^nd International Conference on Tumor & Cancer Immunology and Immunotherapy July 17-18, 2017 Chicago, Illinois, USA

Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. Most tumor markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions. These substances can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily fluids of some patients with cancer. Most tumor markers are proteins. Thus far, more than 20 different tumor markers have been characterized and are in clinical use. Some are associated with only one type of cancer, whereas others are associated with two or more cancer types. There is no “universal” tumor marker that can detect any type of cancer. Among various approaches to specifically target drug-loaded carrier systems to required pathological sites in the body, two seem to be most advanced – passive (EPR effect-mediated) targeting, based on the longevity of the pharmaceutical carrier in the blood and its accumulation in pathological sites with compromised vasculature, and active targeting, based on the attachment of specific ligands to the surface of pharmaceutical carriers to recognize and bind pathological cells.

Interactions between malignant and non-transformed cells create the Tumor microenvironment (TME). The non-malignant cells of the TME have a dynamic and often tumor-promoting function at all stages of carcinogenesis .Intercellular communication is driven by a complex and dynamic network of cytokines, chemokine’s, growth factors, and inflammatory and matrix remodeling enzymes against a background of major perturbations to the physical and chemical properties of the tissue. The evolution, structure and activities of the cells in the TME have many parallels with the processes of wound healing and inflammation, but cells such as macrophages are also found in cancers that have no known association with chronic inflammatory conditions.

Immunotherapy is an innovative treatment approach that empowers the human immune system to overcome cancer and other debilitating diseases. The T-cell therapies are the most radical of several new approaches that recruit the immune system to attack cancers. The treatments work by removing molecular brakes that normally keep the body’s T cells from seeing cancer as an enemy, and they have helped demonstrate that the immune system is capable of destroying cancer. Immunotherapy may help boost the body’s immune response. This approach uses drugs/agents to trigger or stimulate the immune system to react to the invader – in this case, the cancer cells. This is similar to how a cold virus would stimulate your immune system.

Targeted therapies act by blocking essential biochemical pathways or mutant proteins that are required for tumor cell growth and survival. These drugs can arrest tumor progression and induce striking regressions in molecularly defined subsets of patients. Indeed, the first small molecule targeted agent, the BCR-ABL kinase inhibitor imatinib, rapidly induced complete cytogenetic responses in 76% of chronic myelogenous leukemia patients. Further research into the underlying genetic pathways driving tumor proliferation uncovered additional oncoproteins that are critical for tumor maintenance, such as the epidermal growth factor receptor (EGFR), BRAF, KIT, HER (also known as neu and ERBB) and anaplastic lymphoma kinase (ALK). Similar to imatinib, small molecule inhibitors of these kinases have effectuated impressive tumor responses in selected patients, although regressions are commonly followed by the development of progressive disease due to the emergence of drug-resistant variants. Resistance usually involves secondary mutations within the targeted protein or compensatory changes within the targeted pathway that bypass the drug-mediated inhibition. Accordingly, targeted therapies may elicit dramatic tumor regressions, but persistence is generally short-lived, limiting the overall clinical benefit.

The goal of the Cancer Research Program is to make significant improvements in the prevention, early detection, diagnosis and treatment of cancer. It will continue to translate basic research findings into clinical applications together with strategic partners, with the National Centre for Tumor Diseases (NCT) and the nationally active German Consortium for Translational Cancer Research (DKTK) playing key roles. The program is also developing new approaches in the fields of cancer genome and epigenome research, metabolic dysfunction, personalized radiation oncology and ion therapy, molecular imaging, neuro-oncology, individualized cancer medicine and health economics.

Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints." The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cell carcinoma, small cell lung cancer, and several other tumor types.

Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer. This can be done in a couple of ways: Own immune system stimulation, Biological therapy or biotherapy. These advances in cancer immunotherapy are the result of long-term investments in basic research on the immune system—research that continues today. Additional research is currently under way to: understand why immunotherapy is effective in some patients but not in other’s who have the same cancer, expand the use of immunotherapy to more types of cancer, increase the effectiveness of immunotherapy by combining it with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy.

Antibody marks the cancer cell and makes it easier for the immune system to find. The monoclonal antibody drug rituximab (Rituxan) attaches to a specific protein (CD20) found only on B cells, one type of white blood cell. Certain types of lymphomas arise from these same B cells. monoclonal antibodies can also function by attenuating hyperactive growth signals neo angiogenesis. A monoclonal antibody can be conjugated to a radioactive particle that will ensure directed delivery to the cancer cell and slow and long release of the radiation, hence maximizing chances of positive outcome and minimizing non-specific damaging exposure to radiation.

Most of us know about vaccines given to healthy people to help prevent infections, such as measles and chicken pox. These vaccines use weakened or killed germs like viruses or bacteria to start an immune response in the body. Getting the immune system ready to defend against these germs helps keep people from getting infections. Most cancer vaccines work the same way, but they make the person’s immune system attack cancer cells. The goal is to help treat cancer or to help keep it from coming back after other treatments. But there are also some vaccines that may actually help prevent certain cancers. Cancer treatment vaccines are different from the vaccines that work against viruses. These vaccines try to get the immune system to mount an attack against cancer cells in the body. Instead of preventing disease, they are meant to get the immune system to attack a disease that already exists. Some cancer treatment vaccines are made up of cancer cells, parts of cells, or pure antigens. Sometimes a patient’s own immune cells are removed and exposed to these substances in the lab to create the vaccine. Once the vaccine is ready, it’s injected into the body to increase the immune response against cancer cells. Vaccines are often combined with other substances or cells called adjuvants that help boost the immune response even further.

Tumor immunogenicity varies greatly between cancers of the same type in different individuals and between different types of cancer. Immunogenicity, which is the ability to induce adaptive immune responses, has been widely analysed by cancer cell transplantation experiments. If rejection requires prior immunization, those transplanted cancer cells (which are known as progressors) are considered intermediate immunogenic. Failure to reject the tumour following immunization against trans-planted cancer cells classifies them as non-immunogenic.

The mainstay of cancer treatment has historically involved therapies, such as surgery, chemotherapy or radiation that were developed without regard for the patient's immune system. These therapies include nonspecific activation of the immune system using toll‐like receptor ligands, cytokines or immune checkpoint inhibitors, or specific treatments, like monoclonal antibody administration or vaccination, that directly target cancer cells. Perhaps, the most promising specific therapy is the adoptive transfer of genetically engineered tumour‐reactive T cells, an approach that has already proven curative in some patients with metastatic disease. Cumulatively, these new immune‐based approaches have great promise to revolutionise cancer therapy. 

The molecular classification of Tumor is actually arrangement analysis disguised as classification. In a typical gene expression array study, the researcher will look at a cluster of tumors of a specific type. Cluster analysis of the gene expression array values will help discrete the tumors into groups with common expression patterns. Some of these groupings will prove to have a detailed biologic feature (e.g. increased tendency to metastasize, higher response to a chemotherapeutic agent, lengthened existence). Cancers are not just masses of malignant cells but complex ‘rogue’ organs, to which many other cells are recruited and can be degraded by the transformed cells. Interactions between malignant and non-transformed cells create the Tumor microenvironment (TME).

A tumor is an abnormal growth of body tissue. Tumors can be cancerous (malignant) or noncancerous (benign). Tumors are of many types such as Carcinoid tumor, Pituitary tumor, and tumor lysis syndrome. In general, tumors occur when cells divide and grow excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace older ones or to perform new functions. Cells that are damaged or no longer needed die to make room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. Problems with the body's immune system can lead to tumors. Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, but they can be seen in other organs, including the lungs, mediastinum, thymus, liver, pancreas, bronchus, ovaries, prostate, and kidneys .Carcinoid tumors have high potential for metastasis.

Tumorigenesis focuses on the multistep process of tumor Development, the critical progression of which is dependent on sequential accumulation of mutations within tissue cells, only a relatively small subset of which is crucial for malignant transformation, driven by the well-known pathways of tumorigenesis (growth signal self-sufficiency; anti-growth signal insensitivity; apoptosis evasion; unbound replicative potential; sustained angiogenesis; and tissue invasion and [potential metastasis). Tumorigenesis depends on carcinogenesis, but not vice versa, and when we focus on carcinogenesis, our scope rests predominantly with mutation or epimutation acquisition, while when we focus on tumorigenesis, our scope is on the multistep progress of mutated cells in tumor development.

To developing new methods to prevent, detect, and treat cancer. It is through clinical trials that researchers can determine whether new treatments are safe and effective and work better than current treatments. Cancer clinical trials have led to scientific advances that have increased doctors' understanding of how and why tumor’s develop and grow. This knowledge has helped doctors make progress in preventing cancer, diagnosing cancer, slowing or stopping the development of cancer, and finding cancers that have come back after treatment.

Cancer cells behave as independent cells, growing without control to form tumors. Tumors grow in a series of steps. The first step is hyperplasia, meaning that there are too many cells resulting from uncontrolled cell division. These cells appear normal, but changes have occurred that result in some loss of control of growth. The second step is dysplasia, resulting from further growth, accompanied by abnormal changes to the cells. The third step requires additional changes, which result in cells that are even more abnormal and can now spread over a wider area of tissue. These cells begin to lose their original function; such cells are called anaplastic. At this stage, because the tumor is still contained within its original location (called in situ) and is not invasive, it is not considered malignant - it is potentially malignant. The last step occurs when the cells in the tumor metastasize, which means that they can invade surrounding tissue, including the bloodstream, and spread to other locations. This is the most serious type of tumor, but not all tumors progress to this point. Non-invasive tumors are said to be benign. The discovery of tumor stem cells in a range of cancers has created opportunities for researchers to identify these rare cells in both solid tumors and hematologic cancers, as well as to investigate the role of these cells at different stages of disease.The recognition that the cancer cell is in a symbiotic relationship with the tumor microenvironment has created opportunities to study the interactions of cancer cells within the tumor or the host microenvironment.

In cancer research and medicine, biomarkers are used in three primary ways:

• To help diagnose conditions, as in the case of identifying early stage cancers (Diagnostic)
• To forecast how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment (Prognostic)
• To predict how well a patient will respond to treatment (Predictive)

The immune system is the body’s natural defence system. It is a collection of organs, cells and special molecules that helps protect you from infections, cancer and other diseases. Immuno-oncology therapies activate our immune system, making it able to recognise cancer cells and destroy them. Breast cancer is one of the major cancer types for which new immune-based cancer treatments are currently in development. Lung cancer surgery carries risks, including bleeding and infection. Clinical trials are studies of experimental lung cancer treatments. Adult central nervous system tumor is a disease in which abnormal cells form in the tissues of the brain and/or spinal cord. A tumor that starts in another part of the body and spreads to the brain is called a metastatic brain tumor. There are different types of brain and spinal cord tumors such as Astrocytic Tumors, Oligodendroglial Tumors, Mixed Gliomas, Ependymal Tumors, Medulloblastomas, Pineal Parenchymal Tumors, Meningeal Tumors, Germ Cell Tumors, Craniopharyngiom. Advances in Immuno-oncology have given oncologists and their patients reason to be encouraged—the launch of immune checkpoint inhibitors and development of other immunotherapy assets for the treatment of several difficult-to-treat diseases, including metastatic melanoma and non-small cell lung cancer, represents great progress.

The development of methods to propagate immune T-cells, and in particular tumor specific T-cells from the patients with cancer, lead to an important breakthrough; the identification of MAGE-1,a melanoma-specific antigen that stimulates human T-cells in-vitro. With antigen specific T-cells as a reagents, it was possible to clone the MAGE-1 studies showed that the human immune system can respond tumor antigens, and the findings stimulated a productive effort to discover tumor antigens. The result is a long and still-growing list of antigens from a variety of tumor that could serve a variety of tumor’s that could serve as targets for treatment.

Engineered T cells are the result of turning a therapeutic process into a product capable of overcoming checkpoint inhibition, and are the future of adoptive immunotherapy. Cytokine release syndrome,” a storm of molecules generated as the cells fights the cancer. Instead of an antibody, single-chain target domain, he used a human cytokine, IL-13, with a mutation in the sequence that gave high affinity for IL-13 receptor α2. These cells were infused intra cranially, establishing the safety of intracranial administration with some antitumor responses.

Immunotherapy encompasses several different treatment approaches, each of which has a distinct mechanism of action, and all of which are designed to boost or restore immune function in some manner.  This includes: Monoclonal antibodies, Immune checkpoint inhibitors, Therapeutic Cancer vaccines, cytokines, and other non-specific immunotherapies.