Checkpoint Inhibitors

Immune checkpoints proteins and their function

Immune checkpoint proteins are found on immune cells and allow normal immune function to occur by assessing potential targets as “self” by binding to the partner protein, or “foreign” which lack the corresponding protein. Thus, they prevent inappropriate activation of the immune system while ensuring removal of potentially harmful cells.

What are checkpoint inhibitors?

Checkpoint inhibitors are immunotherapy agents, specifically monoclonal antibodies, used in the treatment of cancer that target immune checkpoints. 

The need for such agents arises from a mimicry mechanism employed by some cancer cells that present with proteins that are read as “self” proteins by the immune checkpoint proteins preventing them from activating the immune system to destroy the cancer cell. By using checkpoint inhibitors, immune cells are better able to target these abnormal cells and lead to their destruction.

Examples of checkpoint inhibitor targets

• PD-1 and PD-L1 inhibitors: These drugs target PD-1 proteins on T cells or its corresponding partner protein PD-L1, which is expressed in large numbers by some cancer cells. These immunotherapy agents are used to treat several cancers, including skin cancer, lung cancer, breast cancer, and renal cancer.
• CTLA-4 inhibitors target the cytotoxic T-lymphocyte- associated protein 4 usually found on regulatory T cells to control T-cell proliferation. The inhibitor is used to treat melanoma, as well as other cancers.
• LAG-3 is the newest novel target to be approved for a checkpoint inhibitor. LAG-3, lymphocyte activation gene-3, is expressed on several immune cells including regulatory T-cells, natural killer cells, B cells, and dendritic cells. They are thought to function early in the immune response to suppress immune function. The LAG-3 inhibitor has been approved to treat melanoma in a combination drug that includes a PD-1 inhibitor.

Common side effects of checkpoint inhibitors

As checkpoint inhibitors interfere with normal functioning of immune cells, they can affect the normal cells of the body leading to damage to cells of several organ systems. Common side effects include:

• Diarrhea
• Fatigue
• Cough
• Nausea
• Skin rash
• Lack of appetite
• Constipation
• Muscle and joint pain

Rare but severe side effects include infusion and autoimmune reactions.