nivolumab

WP

Nivolumab is an immunomodulator by blocking ligand activation of the programmed cell death 1 (PD-1) receptor on activated T cells.

Nivolumab, a drug in clinical trials also known as BMS-936558 or MDX1106, is a fully human IgG4 monoclonal antibody developed by Bristol-Myers Squibb for the treatment of cancer.

Nivolumab acts by blocking a negative regulator of T-cell activation and response, thus allowing the immune system to attack the tumor. This is an example of immune checkpoint blockade.

PD-1 is a protein on the surface of activated T cells. If another molecule PD-L1, called programmed cell death 1 ligand 1 or programmed cell death 1 ligand 2 (PD-L1 or PD-L2), binds to PD-1, the T cell becomes inactive.

This is one way that the body regulates the immune system, to avoid an overreaction.

Many cancer cells make PD-L1, which inhibits T cells from attacking the tumor. Nivolumab blocks PD-L1 from binding to PD-1, allowing the T cell to work.

PD-L1 is expressed on 40–50% of melanomas and has limited expression otherwise in most visceral organs with the exception of respiratory epithelium and placental tissue.

Indications

Nivolumab has been approved for the treatment of :
 advanced melanoma
 classic Hodgkin lymphoma

 advanced melanoma

• Nivolumab is used as a first line treatment for inoperable or metastatic melanoma in combination with ipilimumab if the cancer does not have a mutation in BRAF, and as a second-line treatment for inoperable or metastatic melanoma following treatment of ipilimumab and, if the cancer has a BRAF mutation, a BRAF inhibitor.

 metastatic squamous non-small cell lung cancer

• It is also used to treat metastatic squamous non-small cell lung cancer with progression with or after platinum-based drugs.
• ESMO 2016 : neoadjuvant nivolumab is safe and has considerable activity in early stage resectable NSCLC

 renal cell carcinoma

• It also used as a second-line treatment for renal cell carcinoma after anti-angiogenic treatment has failed.

See also

 immune checkpoint inhibitors