Identification of TM4SF1 as a novel tumor-associated antigen in biliary tract cancers targetable by CAR-T cell therapy

Anti-TM4SF1 CAR-T cells show significant anti-tumor activity against biliary tract cancer in a cell line-derived xenograft (CDX) model, supporting TM4SF1 as a targetable tumor-associated antigen.

• Why it matters: Biliary tract cancers have delayed presentation and poor prognosis, and existing tumor-associated antigen targets are limited by expression in normal liver tissue.
• What they did: The study assessed TM4SF1 expression in BTC versus normal hepatic/biliary tissue using TCGA mRNA analyses and immunohistochemistry, then tested anti-TM4SF1 CAR-T cells in vitro co-culture with BTC cell lines and in a CDX model.
• The result: TM4SF1 is significantly upregulated in BTC across anatomical subtypes at both mRNA and protein levels, and CAR-T targeting robustly inhibits BTC growth in vitro and reduces tumor growth in vivo.

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