Research Progress and Optimization Strategies of Bispecific Antibody Therapies for CLDN18.2-Positive Gastric Cancer

CLDN18.2 is specifically overexpressed in gastric cancer tissues and represents an important emerging therapeutic target in gastriccancer treatment. Bispecific antibodies (BsAbs), a class of antibody-based therapeutics capable of simultaneously targeting two antigensites, have recently entered clinical development for the treatment of CLDN18.2-positive gastric cancer. This review systematicallysummarizes the molecular designs, functional subtypes, and clinical development of CLDN18.2-related BsAbs, while analyzing currentchallenges and potential optimization strategies. Currently, CLDN18.2-related BsAbs that have entered clinical development mainlycomprise three categories: T-cell engagers, T-cell costimulators, and immune checkpoint-blocking BsAbs. These agents havedemonstrated preliminary antitumor activity in later-line monotherapy and first-line combination therapy settings, with generallymanageable safety profiles. Optimization of target combinations, precise patient selection, strategies to overcome efficacy limitations, and improved safety management represent important directions for enhancing the therapeutic value of BsAb-based approaches.