Pembrolizumab is a checkpoint inhibitor approved for several cancers. Its mechanism is:
- A Anti-CTLA-4 monoclonal antibody that restores T-cell priming in lymph nodes
- B Anti-PD-L1 monoclonal antibody that removes the 'do not kill' signal from tumour cells
- C Anti-PD-1 monoclonal antibody that blocks binding of PD-L1/PD-L2 to PD-1 on T-cells, restoring cytotoxic T-cell activity in the tumour microenvironment ✓
- D Anti-CD20 monoclonal antibody depleting B-cells in tumour stroma
Correct answer: C. Anti-PD-1 monoclonal antibody that blocks binding of PD-L1/PD-L2 to PD-1 on T-cells, restoring cytotoxic T-cell activity in the tumour microenvironment
Explanation
Pembrolizumab (and nivolumab) are humanised IgG4 anti-PD-1 monoclonal antibodies. They block PD-1 (on T-cells) from interacting with its ligands PD-L1 and PD-L2 (expressed on tumour cells and APC), releasing T-cells from tumour-induced anergy. This allows cytotoxic T-cell reactivation against tumour antigens. Anti-CTLA-4 (ipilimumab) works at the priming phase in lymph nodes. Anti-PD-L1 agents (atezolizumab, durvalumab, avelumab) block the ligand rather than the receptor. Anti-CD20 (rituximab, obinutuzumab) depletes B-cells.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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