Targeting Immune Checkpoints
One of the most groundbreaking approaches in immuno-oncology involves targeting immune checkpoints, which are inhibitory pathways that normally help regulate the immune system and prevent autoimmune disease. However, cancer cells can hijack these checkpoints to evade detection and destruction by the immune system. Immunotherapies known as checkpoint inhibitors work by releasing the brakes on immune responses against cancer. Two key immune checkpoints that have emerged as therapeutic targets are CTLA-4 and PD-1/PD-L1.

CTLA-4 acts as an “off” switch early in T cell activation, preventing T cells from killing cancer cells. Ipilimumab was the first Immuno-Oncology Assays-approved checkpoint inhibitor, blocking the interaction between CTLA-4 and its ligands. This enables T cells to carry out their anti-tumor functions more effectively. However, CTLA-4 blockade can also cause immune-related adverse events by promoting autoimmunity. PD-1/PD-L1 acts later during an immune response to turn off T cell activity and reduce collateral tissue damage. Drugs targeting this pathway, such as nivolumab, pembrolizumab and atezolizumab, have shown impressive results against various cancers including melanoma, lung cancer and bladder cancer. PD-1 inhibitors generally have milder side effects than CTLA-4 inhibitors due to their more specific mechanism of action.

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