The immune system has routinely been the focus of cancer treatments. One of the strategies that targets the immune system is by use of monoclonal antibodies to specifically target tumor antigens leading to immune activation and tumor destruction. Therefore, many biopharmaceutical companies are interested/invested in antibody development, including the development of next-generation antibodies such as bispecific antibodies. The Development Center for Biotechnology (DCB) in Taiwan has developed a new platform for the generation of immunoglobulin kappa chain-bridged single chain bispecific antibody. Using this platform, DCB constructed a kappa domain-bridged HER2/CD3 bispecific single chain antibody known as the LBscbHER2-CD3. Utilizing a mammalian expression system, the antibody can be easily purified by affinity chromatography via kappa fragment capture. Binding affinity studies have revealed that the purified LBscbHER2-CD3 antibody is able to independently as well as simultaneously bind to HER2+ tumor cells and CD3+ T cells at low nanomolar concentrations. In co-culture experiments, the addition of purified LBscbHER2-CD3 antibody resulted in a significant increase in IL-2 production which is a strong indicator of human T cell activation. In addition, the co-engagement of either IL-2 primed or un-primed human T cells and HER2+ tumor cells by the LBscbHER2-CD3 antibody facilitated the killing of tumor cells from breast, colon and pancreatic cancers. Lastly, when administered in vivo, LBscbHER2-CD3 showed strong tumor growth inhibition in SCID mice xenograft models with implanted HER2+ SW480 cancer cells, HT29 human colon carcinoma cells, and Capan-1 human pancreatic cancer cells. In conclusion, the LBscbHER2-CD3 bispecific antibody has strong affinity for both the cancer cell-expressing receptor and the T cell antigen which leads to cancer cell elimination in vitro and in vivo. These results suggest that LBscbHER2-CD3 may have therapeutic potential for drug development in the treatment of human cancers.
Citation Format: Yu Hsun Lo, Jei-Hwa Yu, Yu-Hsen Hsui, Ta-Tung Yuan. Developmental and functional characterization of immunoglobulin kappa chain-bridged single chain bi-specific antibody for targeted antitumor therapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B018.
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