Abstract 524: Discovery of NKp46 antibody for NK cell engager using common light chain phage display approach

Abstract

Abstract NK cells express activating receptors such as CD16a (FcγRIIIA), NKG2D, SLAM family members and the natural cytotoxicity receptors (NCRs). Full activation of NK cells require co-engagement of different activating receptors. NKp46, a member of NCRs, is a 46 kDa glycoprotein and belongs to immunoglobulin (Ig) superfamily, NKp46 is frequently expressed on tumor infiltrating lymphocytes. Activation of NKp46 with antibody triggers not only NK cell cytotoxicity but also cytokine release. Taken together, NKp46 is a promising target for anti-tumor therapy. Here we described the discovery of fully human NKp46 antibody by phage display approach with common light chain and naïve human B cell library. Bispecific antibody has been researched for many years and very limited number of bispecific antibodies are currently in the market. Heavy and light chain miss pairing is the bottleneck of bispecific antibody discovery and development. To overcome the hurdle, we generated a fully human common light chain phage display library with two commonly used light chain sequences combined with heavy chain fragment from human naïve scFv library. Two light chain sequences were selected based on the approved antibodies sequences and the expression levels. The phage library was then used for panning against recombinant human NKp46 extracellular domain protein and CHOK1 cells overexpressing human NKp46. After conversion to full IgG format, 4 candidates bind specifically to NKp46 and cross react with both human and cyno NKp46. Affinities of the candidates were comparable to bench mark antibodies as determined by FACS. To summarize, we have generated fully human common light chain phage display library that can be used for bispecific antibody discovery. The anti-NKp46 antibodies discovered can be further developed for NK cell engager and NK cell redirecting bispecific antibody. Citation Format: Teddy Yang, Seng Zhu, Jing Gao, Jingyun Yao, Xumin Gong. Discovery of NKp46 antibody for NK cell engager using common light chain phage display approach [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 524.