OnCo
ideasIdea

In vivo CAR-T against solid-tumour antigens

If a lipid nanoparticle can make CAR-T cells inside the body for lymphoma, it could be redosed weekly against solid-tumour targets that autologous CAR-T cannot sustain.

Solid-tumour CAR-T fails partly from exhaustion and poor persistence of a single infused product. Transient, redosable in vivo CAR expression could deliver repeated waves of fresh effector cells.

Confidence
10%30%likelyOnCo editors (initial estimate), 2026-09-07 · In vivo CAR is first-in-human in B-cell disease only; solid-tumour antigen and trafficking problems remain.
Hypothesis
Weekly in vivo CAR mRNA-LNP against CLDN18.2 or GPC3 produces response rates comparable to ex vivo CAR-T with lower toxicity and no manufacturing delay.
Rationale
Transient expression limits on-target off-tumour toxicity; repeated dosing avoids exhaustion of a single product; no lymphodepletion needed.
What would test it
Phase 1 in CLDN18.2+ gastric cancer after satri-cel proof of concept; measure CAR+ T-cell frequency, tumour infiltration, and toxicity per dose.
Maturity
speculative

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