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‹ Sat · 1 Aug 2026
Novel or significantly improved treatment

CPNE1 promotes stemness and confers resistance to GPC3 CAR-T cell therapy in hepatocellular carcinoma via the STAT3-TGF-β signaling pathway.

Silencing one gene restores CAR-T cell function against liver cancer and strengthens immune infiltration without systemic toxicity.

CPNE1 overexpression in HCC drives T-cell exhaustion via STAT3-TGF-β signaling; CPNE1 knockdown restores GPC3-targeted CAR-T cell function, enhances intratumoral T-cell infiltration, and improves antitumor efficacy without systemic toxicity; high CPNE1 correlates with poor ICI outcomes clinically. This record was retained from the prior triage attempt for PubMed pipeline handoff.

What the study was

Study design
experimental (mechanistic, in vitro + in vivo)
Category
novel_therapeutics
Maturity
Exploratory
Journal
J Immunother Cancer

Why it surfaced

Directly addresses CAR-T resistance in HCC—a major barrier to solid tumor CAR-T therapy; J Immunother Cancer (premier immunotherapy journal); integrative mechanistic + clinical correlate; CPNE1 is a novel, actionable resistance node distinct from known mechanisms.

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