YH004 4-1BB

YH004 is a novel humanized antibody targeting 4-1BB, a member of the tumor necrosis factor receptor superfamily, on the surface of immune cells, using a unique IgG1 subtype. 4-1BB is mainly expressed in T cells, DC cells, monocytes, B cells, mast cells, NK cells and neutrophils. As a 4-1BB agonist, YH004 can induce immune cell proliferation and cytokine expression to activate the body’s immune response. In vivo preclinical experiments in mice showed that the single-drug and combined drug efficacies of YH004 were significantly better than those of the control. A large number of preclinical and clinical data have demonstrated the great potential of targeting 4-1BB for cancer immunotherapy, but the hepatotoxicity caused by 4-1BB agonists has hindered its further clinical development. In vitro functional analysis of YH004 showed that its binding affinity to human and monkey 4-1BB was equivalent, and no hepatotoxicity of YH004 was observed in in vivo toxicity tests of cynomolgous monkeys. YH004 was recently approved for Phase I clinical trials in Australia.

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