VHH-based CAR-T cells targeting Claudin 18.2 show high efficacy in pancreatic cancer models

About the Article:

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, with survival rates below 10% and few effective treatment options. Claudin 18.2 (CLDN18.2) has emerged as a promising tumor‑specific target for immunotherapy.

This article reports on engineered VHH‑based CAR‑T cells, using a single‑domain antibody (VHH) as the antigen‑binding domain that demonstrate potent anti‑tumor activity against CLDN18.2‑expressing pancreatic cancer in preclinical models. These next‑generation constructs show strong cytokine responses and sustained cytotoxicity, highlighting their potential to overcome limitations of traditional scFv‑based CAR‑T designs.

Unlike traditional CAR-T constructs, these VHH-based versions, utilizing single-domain antibodies, offer enhanced stability, reduced immunogenicity, and potent cytotoxic activity. The results show:

• Sustained cytokine release
• Effective tumor eradication in vitro and in vivo
• Promising safety and specificity profiles

This study adds to the growing body of work demonstrating the potential of next-generation CAR-T cell therapies for solid tumors like pancreatic cancer.

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