Cancer Immunotherapy and its Checkpoints

Checkpoints within the body ensure regulation of various hormones, receptors, and responses in order to keep the body running optimally. They allow the body to get rid of foreign invaders without destroying healthy cells. The key to reducing the risk and potentially curing many cancers is through targeting the various checkpoints found within the immune system. When cancer is present, these checkpoints, or co-inhibitory receptors, may be unregulated allowing the development and spread of cancer throughout the body.

The immune response is be modulated by T-cells. Activated T-cells efficiently allow for the anti-tumor immune response and keeps everything in check. T-cells are typically activated when a T-cell recognizes an antigen on the surface of the antigen presenting cell (APC). T-cells can be inhibited to minimize the immune response including dampening inflammation. Here, T-cell receptors bind to inhibitory receptors on (APCs). In chronic ailments, such as infections and cancer, T-lymphocytes in the body are constantly released causing a depletion of T-cells known as a state of exhaustion. This exhaustion shows as a gradual loss of effector functions and cytokine production, increasing the expression of multiple inhibitory receptors. PD-1 is a member of the immunoglobulin gene superfamily and plays a regulatory role in inhibiting T-cell activation and function. This pathway is critical in inhibiting viral antigen-specific CD8 T-cells in HIV, HCV, and HBV infections. T-cell function can be restored by a PD-1 blockade.



Suppression of T-cell proliferation can occur by the interaction of PD-1/PD-L1. This mechanism allows cancer cells to evade detection and inhibit the anti-tumor immune response. This allows for unchecked cancer proliferation. Cancer immunotherapy strategies block these pathways through checkpoint inhibiting antibodies such as PD-1 and LAG-3. Inhibiting these checkpoint pathways leads to an active immune response against cancer cells. Lag-3 resembles CD4 with high homology and also binds to MHC class II with a higher affinity. Like the PD-1 pathway, it has a role in the negative regulation of T-cell response and is a target for immunotherapy. Expression of Lag-3 is increased in exhausted T-cells due to cancer and chronic viral infections. A blockade of Lag-3 removes the suppressor function of regulatory T-cells and enhances immune response. PD-1 and Lag-3 are co-expressed on many animal models of cancer such as, exhausted virus-specific CD8+ T-cells, and on both CD4+ and CD8+ tumor infiltrating lymphocytes. Current research is being explored to block both signaling pathways cooperatively for clinical cancer therapy.





These checkpoints and known antibodies/proteins provide clinically validated treatments for many cancers. Cancer immunotherapy and other immunotherapeutic strategies include cancer vaccines, oncolytic viruses, ex-vivo activated T and natural killer cells, and the administration of co-stimulating or blocking antibodies. In 2010, autologous cellular immunotherapy, sipuleucel-T, was used to treat prostate cancer. Next came the approved use of the CTLA-4 antibody, ipilimumab, in 2011 and PD1 antibodies for melanoma cancers in 2014. With these clinical accomplishments, researchers continue to unveil new immune pathways that can be manipulated to attack the invading cancer cells. Antibodies for immune pathways such as PD-1, Lag-3 and CD40 are on the forefront of cancer immunotherapy and has already been put in use to benefit thousands of people. As research and development continues, the therapy can only become more enhanced.

Enzo develops innovative assays and reagents in the fields of epigenetics, autophagy, and Wnt research. These novel tools, part of a broad portfolio of products established for decades in peer-reviewed literature, will help support cancer discovery into the next decade, and beyond. We also have our SCREEN-WELL® Cancer Library, a collection of 275 compounds that can be used for screening and assay development. Our portfolio also includes kits, antibodies and proteins including PD-L1, PD-1 and MEGACD40L® to aid your research. Please check out our Cancer and Immunology platforms for more information or contact our Technical Support Team for further assistance.

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