Immune checkpoint

Immune checkpoint inhibitors

Monoclonal antibodies are a type of cancer immunotherapy that have been developed to target immune checkpoints.

Drug toxicities include:

• Gastrointestinal
• Dermatologic
• Endocrine
• Exacerbation of pre-existing autoimmune disease.

PD-1 inhibitors

These antibodies target the Programmed Cell Death 1 Receptor (PD-1 Receptor). Programmed Cell Death Type I is also known as apoptosis. The PD-1 Receptor is "an inhibitory T-lymphocyte receptor that has specificity for CD274 antigen and Programmed Cell Death 1 Ligand 2 Protein."

Pembrolizumab was approved by the FDA for “patients with unresectable or metastatic, microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) solid tumors, regardless of tumor site or histology”.

Nivolumab may case drug toxicity in about 40% of patients - rash and diarrhea are the most common effects.

Examples:

• Pembrolizumab (Keytruda)
• Nivolumab (Opdivo)

PD-L1 inhibitors

• Atezolizumab (Tecentriq)
• Avelumab (Bavencio)
• Durvalumab (Imfinzi)

CTLA-4 blockade

The CTLA-4 Antigen is "an inhibitory T cell receptor that is closely related to CD28 antigen. It has specificity for CD80 antigen and CD86 antigen and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing peripheral tolerance."

Ipilimumab may cause autoimmune pituitary disease and exacerbate autoimmune disease in recipients with pre-existing autoimmune disease. The U.S. FDA has issued guidance on managing side effects.

Examples:

• Ipilimumab (Yervoy)

Raf protein kinase inhibitors

Raf inhibitors are "a family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF kinases. They are MAP kinase kinase kinases that play important roles in signal transduction."

Examples:

• Vemurafenib

See also

• Cell cycle checkpoint