OnCo
ideasIdea

Regionally delivered mesothelin CAR-T with PD-1 blockade

Deliver engineered T cells directly into the chest cavity where mesothelioma grows, and give immunotherapy to keep them working.

Intrapleural mesothelin CAR-T (MSK, Adusumilli) with pembrolizumab produced responses and long survivors in a phase 1 study; regional delivery avoids on-target lung toxicity and improves trafficking.

Hypothesis
Intrapleural mesothelin CAR-T plus PD-1 blockade achieves median OS beyond 24 months in relapsed mesothelioma, exceeding historical second-line outcomes.
Rationale
Mesothelin is near-universally expressed; the pleural space is accessible; CAR-T exhaustion is reversible with checkpoint blockade in preclinical models.
What would test it
Phase 2 with a contemporaneous control (second-line chemotherapy or nivolumab), OS endpoint; armoured (PD-1 dominant-negative) CAR-T variant as a second arm.
Maturity
early clinical

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