The ICB study has made great progress in the field of clinical tumor therapy, among which the monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed death receptor 1 (PD-1) signaling pathway-specific immune checkpoints have significant efficacy in the field of tumor therapy. CTLA-4, also known as CD152, was discovered in 1978 as the first immune checkpoint blockade available for anticancer therapy, generally expressed on activated CD4+ and CD8+ T cells and exerting a negative regulatory role in the initial T cell activation.
Mechanism of Action
CTLA4 has high homology to the costimulatory molecule (CD28) on the T cell, and both has the same ligand CD86 (B7-2) or CD80 (B7-1), but reverse functions. Binding of CTLA-4 to B7 molecules can inhibit T cell activation. Therefore, blockade of the immune checkpoint B7/CTLA-4 can enhance tumor-specific T cell activation. CTLA4 is highly expressed on Treg cells, and some anti-tumor activity can also be achieved by eliminating Treg cells. YH001 targeting CTLA-4 can enhance the removal of regulatory T cells (Treg cells) in the tumor microenvironment by improving the immune response against tumor cells in order to treat multiple tumors. Enhancing patients' immune responses to tumors by blocking inhibitory signals of human anti-tumor responses is considered the most promising tumor immunotherapy at present. Guided by this theory, CTLA-4 and PD-1 are considered as two significant checkpoints of the immune system, as well as cornerstone targets for tumor immunotherapy as they initiate anti-tumor immune attacks by affecting different types of T cells, respectively.
YH001 is a recombinant humanized anti-CTLA-4 IgG1 monoclonal antibody injection developed by Eucure (Beijing) Biopharma Co., Ltd. Preclinical data demonstrated that binding to CTLA-4, activation of CD28 signaling and induction of ADCC activity of YH001 were higher than that of ipilimumab under the same conditions; binding of CTLA-4/CD80 and CTLA-4/CD86 was similar to that of Ipilimumab, so YH001 is predicted to have a good anti-tumor effect.
Clinical Study for CTLA-4
In May 2020, the first patient screening was completed for Phase I clinical study of YH001 in combination with Junshi Biosciences' anti-PD-1 monoclonal antibody in Australia.