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An important part of the immune system is its ability to distinguish between normal cells in the body and cells that it considers to be “foreign”. This allows the immune system to attack foreign cells away from normal cells. To do this, it uses “checkpoints”-some molecules on immune cells that need to be activated (or inactivated) to initiate an immune response. Checkpoint inhibitors are also described as a monoclonal antibody or targeted therapy.
Examples of Checkpoint Inhibitors
- PD-1 or PD-L1 inhibitors
- CTLA-4 inhibitors
PD-1 is a checkpoint protein on immune cells called T cells. It usually acts as a “shutdown switch” to help prevent T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal and cancer cells. When PD-1 binds to PD-L1, it basically tells T cells to stay away from another cell. Some cancer cells contain large amounts of PD-L1, which helps them escape immune attacks. Monoclonal antibodies against PD-1 or PD-L1 can block this binding and enhance the immune response to cancer cells. These drugs show great potential in the treatment of certain cancers.
CTLA-4 is another protein on some T cells that acts as a “shutdown switch” to maintain control of the immune system. CTLA-4 can suspend the response of activated T cells to (T cell response) and mediate the inhibitory function of Treg. Using a mouse model of bladder cancer, the researchers found that local injection of low doses of anti-CTLA-4 antibody into the tumor area had the same ability to inhibit the tumor as it did when the antibody was transported in the blood. At the same time, the level of circulating antibody is also low, that is, the effect of local injection of anti-CTLA-4 is the same as that of anti-CTLA-4 antibody injected in blood. At the same time, the level of antibody in circulation is also low, suggesting that local application of anti-CTLA-4 treatment can reduce adverse reactions.
The clinical success of immunosuppressive agents has brought new life to the immunotherapy of cancer. What we need to do in the future is how to improve the efficiency of immune checkpoint blocking and immune checkpoint inhibitor combination therapy to enable patients who cannot be treated with single blocker to obtain a lasting anti-tumor response. How to develop an effective combination of immune checkpoint blocking therapy to increase efficacy and reduce side effects. Tumors use a variety of means to escape immune elimination, so it is necessary to better understand the immunosuppression of tumor microenvironment.
1. Mahoney, K. M., Freeman, G. J., & McDermott, D. F. (2015). The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clinical therapeutics, 37(4), 764-782.
2. Hui, E. (2019). Immune checkpoint inhibitors. J Cell Biol, 218(3), 740-741.