Luye Pharma Group’s subsidiary Boan Biotech recently published research results for its innovative in-house bispecific antibody BA1202 (CEA/CD3 bispecific T-cell engager) in Antibody Therapeutics.
Screenshot of the article (image credit: Antibody Therapeutics)
Published by Oxford University Press, Antibody Therapeutics is a peer-reviewed journal under the Chinese Antibody Society. The journal provides a forum for publicizing the latest advances in the global R&D and commercialization of therapeutic antibodies.
As a tumor biomarker and tumor associated antigen, CEA (Carcinoembryonic antigen) is highly expressed in colorectal cancer, gastric cancer, pancreatic cancer, lung cancer, breast cancer and other solid tumors, and its expression correlates with disease progression.
T cell engager antibodies that are designed to target tumor antigens and T cell CD3 are one of the most active fields in the development of bispecific antibodies. They can effectively kill tumor cells expressing tumor-associated antigens, increase the infiltration of immune cells in tumor tissues, and convert cold tumors into hot tumors. If combined with immune checkpoint inhibitors, it can improve efficacy especially for cold tumors.
However, the current development of CD3 antibodies is still facing many challenges, including the toxicity of the cytokine storm caused by high affinity CD3 binding of T cells, and the short half-life of early-approved antibodies in the human body.
To make the CEA-CD3 bispecific antibody, Boan Biotech scientists in the Boston R&D center adopted a new symmetrical butterfly format that retains the Fc region with Fc silencing mutations. This antibody format exhibits bivalent binding to tumor antigen and monovalent binding to CD3 on T cells, which is critical in minimizing target independent T cell activation. Importantly, the team has successfully optimized CD3 affinity to reduce cytokine release.
The highlights of the article include:
· While binding affinity to CD3 is reduced, it does not affect the killing activity against target cells, but secretion of cytokines is greatly reduced. Therefore, it is expected to reduce CRS toxicity.
· It has shown efficacy in the colorectal cancer model, and complete response was observed. In addition, it showed a clear dose-dependent anti-tumor activity with anti-tumor activity at 0.1 mg/kg.
· Compared with other CEA/CD3 antibody drugs under development, our CEA-CD3 showed stronger in vitro activity and in vivo efficacy (data not yet published).
· There was a synergistic anti-tumor effect with anti-PD-L1 Atezolizumab; this was accompanied by a substantial increase in T cell infiltration in the tumor.
· The CEA-CD3 antibody shows high specificity in binding to certain tumor tissues but not to normal tissues in the IHC staining.
Dr. Li Zhou, the corresponding author of the article and VP of Boan Biotech, added: "We have established a unique CD3 bispecific antibody platform. Compared with similar products that are under development, our CEA-CD3 bispecific antibody demonstrated strong efficacy in vivo and reduced cytokine release. We will accelerate product development in the hope of providing effective and safe treatment options for cancer patients as soon as possible."
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