CELL INTELLIGENCE · 肿瘤细胞治疗研究

INTRODUCTION: The tight junction protein Claudin-18.2 (CLDN-18.2) has been identified as a novel drug target for various solid tumors, including biliary tract cancers (BTC). Antibody-based approaches to target CLDN-18.2 have shown promising results in early clinical trials and several novel modalities like antibody-drug conjugates, bispecific T-cell engagers or CAR T-cells are currently also explored. AREAS COVERED: This review discusses the translational knowledge and gaps related to the underrepresentation of BTC in early clinical (basket) studies. We outline the current status of early clinical trials of drugs targeting CLDN-18.2 in BTC and discuss the need to determine prevalence and cutoff data in larger cohorts to overcome limitations related to clinical and molecular heterogeneity of BTC. EXPERT OPINION: Targeting CLDN-18.2 is a promising novel approach to treat solid tumors, including BTC. To confirm encouraging first clinical data, larger studies specific for BTC are needed to address tumor heterogeneity and to determine cutoff levels of CLDN-18.2 expression. Such studies are also needed to understand combination options and sequencing of therapies and to further validate novel approaches to fully exploit the potential of targeting CLDN-18.2 in BTC.