- Mechanism of Action
- A monoclonal antibody directed against programmed cell death protein 1 (PD-1), a surface co-inhibitory receptor on circulating activated T cells, B cells and NK cells.
PD-1 binds to two ligands (PD-L1 and PD-L2) and inhibit T cell receptor signalling, downregulating immune responses and promoting tolerance
Many tumours express or overexpress PD-L1.
Binding of anti-PD1 monoclonal antibodies to PD-1 leaves the ligand unable to bind, and therefore stimulates an ongoing immune response.
- Certain solid organ and haematologic malignancies with high levels of microsatellite instability (MSI). Malignancies of particular interest are melanoma, non-small cell lung cancer, renal cancer and bladder cancer, though this is a rapidly growing field.
- Adverse Effects
- Endocrinopathies - thyroiditis, adrenalitis, hypophysitis, diabetes mellitus
- Pulmonary toxicity - pneumonitis
- Hepatotoxicity - hepatitis, LFT derangement
- GI toxicity - colitis
- Rheumatological - flares of previous disease, PMR, arthralgias / myalgias
- Skin - maculopapular rash, Stevens-Johnson syndrome, Sweet syndrome
- Peripheral neuropathy
- Nausea / vomiting / diarrhoea
- Infections (particularly upper respiratory tract infection)
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