Immune checkpoint inhibitor

Immune checkpoint inhibitors are a class of drugs used primarily in oncology to treat a variety of cancers by enhancing the body's immune response against tumors. These drugs target molecules known as immune checkpoints, which are used by cancer cells to evade the immune system.

Mechanism of Action

Immune checkpoints are regulatory pathways in the immune system that either turn up a signal (co-stimulatory molecules) or turn down a signal (inhibitory molecules). In cancer, these checkpoints are often manipulated by tumor cells to avoid being attacked by the immune system. Immune checkpoint inhibitors work by blocking these inhibitory molecules, thus allowing T-cells to effectively attack cancer cells.

The most well-known targets of these inhibitors are the programmed cell death protein 1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). By inhibiting these proteins, immune checkpoint inhibitors help restore the immune system's ability to detect and destroy cancer cells.

Clinical Use

Immune checkpoint inhibitors have been approved for the treatment of several types of cancer, including melanoma, non-small cell lung cancer, kidney cancer, bladder cancer, and head and neck cancers. These drugs have significantly improved the prognosis for many patients, offering longer-lasting responses compared to traditional therapies like chemotherapy.

Types of Immune Checkpoint Inhibitors

The most commonly used immune checkpoint inhibitors include:

• Nivolumab (Opdivo) – targets PD-1
• Pembrolizumab (Keytruda) – targets PD-1
• Atezolizumab (Tecentriq) – targets PD-L1
• Ipilimumab (Yervoy) – targets CTLA-4

Side Effects

While immune checkpoint inhibitors have revolutionized cancer treatment, they can also cause a range of side effects due to their mechanism of enhancing the immune response. These side effects can vary from mild to severe and include fatigue, skin rash, colitis, hepatitis, endocrinopathies, and pneumonitis. Management of these side effects is crucial for the safe use of these therapies.

Future Directions

Research continues to explore new immune checkpoints and the development of next-generation inhibitors. Combination therapies involving immune checkpoint inhibitors and other treatments such as vaccines, targeted therapies, and radiotherapy are also under investigation to enhance efficacy and overcome resistance.

See Also

• Cancer immunotherapy
• Monoclonal antibodies
• Oncolytic virus