YH003 is a novel humanized antibody targeting CD40, a member of the tumor necrosis factor receptor superfamily, on the immune cells. YH003 promotes the activation of innate immune cells such as dendritic antigen presenting cells (DCs) by specifically activating CD40 receptor signaling pathways to positively regulate the effector activity of anti-tumor T cells. Studies to date demonstrated that activation of CD40 is a key regulator of tumor immunotherapy that effectively translates cold tumors lacking immune cell infiltration into hot tumors with good response to tumor immunotherapy.
Mechanism of Action
CD40 (cluster of differentiation 40) is expressed in APC cells, such as dendritic cells (DCs), B cells, monocytes, and many nonimmune cells and extensive tumors. Interaction of APC with its trimer ligand CD154 on activated T helper cells leads to activation of APC, which has been found to be essential in mediating many immune and inflammatory responses, including T cell dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Agonistic CD40 antibodies have been shown to activate APCs, promote anti-tumor T cell responses, and culture cytotoxic bone marrow cells with the potential to control tumor growth in the absence of T cell immunity. Agonistic CD40 antibodies have also been shown to activate tumor-killing macrophages and indirectly activate natural killer (NK) cells. Binding of CD40L to CD40 on endothelial cells stimulates the production of cytokines and chemokines, and may promote tumor infiltration by immune cells such as T cells.
Clinical Study for CD40
In May 2020, the first patient screening was completed for Phase I clinical study of YH003 in combination with Junshi Biosciences' anti-PD-1 monoclonal antibody in Australia, and is expected to enter the dose escalation and expansion of Phase II in June 2020.