Claudin 18.2 (CLDN18.2) is a gastric-specific membrane protein, and is believed to be an ideal tumor antigen for immunotherapy. I-Mab and ABL Bio co-develop a bispecific antibody CLDN18.2-4-1BB (TJ-CD4B). TJ-CD4B showed strong tumor growth inhibition (TGI) of CLDN18.2 expressing tumor cells, with an increase of tumor infiltrating lymphocytes. Our data suggested TJ-CD4B activated 4-1BB in a CLDN18.2-dependent manner, thus addressing the safety concern associated with 4-1BB-based therapies. TJ-CD4B is a promising IO therapeutic option for gastric and other CLDN18.2-positive tumors.