Advances in Immuno-Oncology
Cancer and Immunotherapy
Cancer is one of the leading causes of deaths worldwide. Standard of care consisting of radiation, chemotherapies, and surgical resections provide limited relief for most cancer patients due to their non-specific approach and related toxicities. While targeted therapies have emerged, innovative cancer treatments are urgently needed for patients with late-stage and refractory disease. Recent advancements in cancer immunology have produced several new approaches that can stimulate the immune system against the tumor or inhibit immune-suppressive signals by cancer cells. While these novel immunotherapies may generate a more potent and durable response than standard treatments, their efficacy is however limited to a subset of patients.
Cancer is a disease of the genome; it is the result of the gradual accumulation of genetic mutations that successively increase cell proliferation. In general, cancer cells have more genetic mutations than normal cells, but each person’s cancer has a unique combination of genetic alterations. Leveraging the advances of Next Generation Sequencing, we can now rapidly generate increasingly comprehensive genetic maps of tumor cells and by comparing to the genetic map of the normal cells of the patient, identify the entire maps of the tumor mutational burden (mutanomes). These mutanomes have brought to our attention the enormous diversity of unique mutations in each tumor. Such unique genetic variations in mutanomes infer that a one-size-fits-all modality is outdated. Our approach is to develop highly personalized or precision immunotherapies based on the unique genetic makeup of each patient tumors.
What are Neoantigens?
Neoantigens are newly formed antigens that have not been previously recognized by the immune system. Neoantigens can arise from altered tumor proteins formed as a result of genetic mutations or from viral proteins. Cancer cells harboring inherent genetic instability, form new antigens (so-called neoantigens) that present their “non-self” neoepitopes, which have not been previously recognized by the immune system. These "non-self" targets allow for a novel approach of precision immunotherapy by targeting tumor specific neoepitopes.
Neoantigens are presented through two classes of MHC’s: Class I for intracellular protein display towards cytotoxic (effector) CD8+ “Killer” T cells, and Class II for extracellular protein display towards CD4+ “Helper” T cells. Both types of T cells, CD8+ and CD4+, are required for driving an effective cancer immunotherapy.