The immune system is responsible for safeguarding the human body from both external and internal threats. Chronic illness results when the immune system is overcome, circumvented, or functions abnormally. Immunotherapy research studies how immune system functionality can be restored or augmented via exogenous modulation in order to combat disease. This is particularly important for cancer research, as tumorigenesis and metastasis hinges upon the cancer cell’s ability to evade the immune system.
Immunotherapeutic approaches can be agent-based or cell-based. In agent-based approaches, immunomodulatory molecules, such as cytokines or antibodies, are introduced in order to either stimulate immune system activity or to mark cancer cells for immune-mediated killing. In contrast, cell-based approaches directly modulate cells via in vitro stimulation or genetic engineering. Following these manipulations, the most effective of the cells can be selected for and expanded prior to therapeutic use.
Immunotherapy focused specifically on combatting cancer is termed immuno-oncology. Numerous immuno-oncology strategies are currently being pursued, with a focus on countering cancer cell immunoevasion mechanisms.
Under physiological circumstances, immune responses need to be suppressed after the threat has been eliminated in order to prevent chronic inflammation and/or autoimmune disorder development. As such, immune cells typically contain suppression signaling pathways mediated by “checkpoint” proteins. Cancer cells are able to activate these checkpoint pathways, especially on T cells, in order to evade cytotoxic killing mechanisms. Immunotherapy strategies can prevent this from taking place, for example, by downregulating the expression of checkpoint proteins or by introducing antagonist molecules to block the binding site without triggering downstream signaling.
Another method by which cancer cells can evade the immune system is to become less antigenic. If a cancer cell does not express a recognizable antigen, a T cell cannot identify and eliminate it. To circumvent this, researchers are creating genetically engineered T cells containing chimeric antigen receptors (CARs) designed to target ubiquitously expressed receptors specific to cancer cells. CAR-T cell therapy is just one strategy using adoptive cell transfer, where a patient’s immune cells are removed from the body, augmented, and then re-introduced. This not only boosts the immune response, but also limits potential autoimmune and rejection issues.
Alternatively, agent-based methods can target cancer cells directly, without modulating immune cell function. One such method involves the usage of custom-engineered therapeutic antibodies. Here, cytotoxic agents are attached to antibodies designed to bind cancer cell-specific antigens. The antibodies are thus able deliver their deadly payload directly and selectively to cancer cells, with ideally minimal collateral damage.
Immuno-oncology research helps further our understanding of the interplay between immune and cancer cells, it refines and improves existing therapeutic strategies, and drives the identification and discovery of new potential targets.
For additional information, please visit our expanded immunotherapy section or explore other specific areas of immunotherapy below.