Immunotherapy

01Releasing the brakes

T cells carry checkpoint receptors that prevent overactivation. CTLA-4 dampens T-cell priming in lymph nodes; PD-1 dampens T cells in tissues when it binds PD-L1, which many tumors display. Antibodies that block these — ipilimumab (anti-CTLA-4), nivolumab and pembrolizumab (anti-PD-1) — let T cells attack.

Responses can be durable for years, especially in melanoma, lung cancer and tumors with high mutation burden or MSI, which display many foreign-looking neoantigens.

02Engineering T cells

CAR-T therapy takes a patient's T cells, engineers them to express a chimeric antigen receptor (often against CD19 on B cells), expands them and infuses them back. It can cure some relapsed leukemias and lymphomas.

Side effects reflect overactive immunity: cytokine release syndrome, neurotoxicity, and autoimmune inflammation of the colon, skin, lungs or thyroid.

Key takeaways

✦Anti-CTLA-4 and anti-PD-1/PD-L1 release T-cell brakes.
✦High mutation burden and MSI predict better checkpoint response.
✦CAR-T redirects a patient's own T cells against a surface antigen.

Watch outCheckpoint inhibitors don't attack the tumor directly — they unblock the patient's T cells.

Quick check

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1.Pembrolizumab blocks…

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