Abstract 1527: KY-CLC-mouse, a common light chain bi-specific antibody discovery platform

Abstract Bi-specific antibody (BsAb) is an attractive therapeutic antibody format for treating different diseases. The matching of light chains is the central issue of BsAb manufacturing. Here we developed a Common Light Chain mouse named KY-CLC-mouse. KY-CLC-mouse has no λ light chain expression with an identical κ light chain. This identical κ light chain was modified from a light chain that frequently appeared in mice and paired with different heavy chains. This light chain had good solubility and stability. It was also easy to humanize without post-translation modifications within CDRs. And the CDRs were modified to decrease immunogenicity. The mouse was validated by developing different monoclonal antibodies against various antigens with an identical light chain and high affinity. Mouse monoclonal antibodies against PD1, LAG-3, PD-L1, CD47, cMET, and EGFR were generated from the hybridoma of KY-CLC-mouse, with KD ranging from 0.1nM to 10nM. Humanized antibodies were derived from the above antibodies with high affinity. BsAb binding two of the above targets were generated by Knob-into-Hole (KiH) technology, such as fully humanized PD1xLAG-3 and CD47xPD-L1 BsAb. PD1xLAG-3 BsAb was simultaneously bound to PD1 and LAG-3 with a blockade of binding to their ligands, PD-L1 and MHCII. CD47xPD-L1 BsAb was simultaneously bound to CD47 and PD-L1 and inhibited their binding to ligands, SIPRα and PD1. Both BsAbs had typical mouse PK with a half-life longer than seven days. The above results indicated that KY-CLC-mouse is an efficient platform for discovering therapeutic antibodies with a common light chain. Citation Format: Hao Peng, Feng Hao, Guojin Wu, Feng He, Jinying Ning. KY-CLC-mouse, a common light chain bi-specific antibody discovery platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1527.