Abstract 5333: NeoMab: A novel platform for fully human therapeutic antibody development

Abstract

Abstract Antibodies and antibody containing therapeutics, such as multivalent antibodies, chimeric antigen receptors (CARs), and antibody directed conjugates (ADCs), have been proven to be highly prominent in cancer treatment. However, challenges such as immunogenicity stemming from non-human or unnatural sequences and limitations in preclinical animal study systems still impede the rapid development of antibody drugs. To overcome these hurdles, GemPharmatech has created a novel antibody gene humanized model, the NeoMab mouse, to develop fully human antibodies. The NeoMab model was established via large genomic fragment knock-in technology, retaining native mouse constant region encoding genes and regulatory elements, while incorporating human variable gene repertoires into the endogenous loci. Developed in the BALB/c background, the NeoMab mouse carries fully functional MHC molecules, potentially enhancing antigen presentation. These mice sustain a competent immune system with a B cell development and maturation pattern, immune cell profile, and serum immunoglobulin levels comparable to those of BALB/c mice. NeoMab mice exhibit a robust humoral immune response, with a rapid increase in antigen-specific serum titers upon immunization using different antigens, such as recombined protein, plasmids, and overexpressing cell lines. Utilizing human V(D)J genes to encode immunoglobulins at a human-like frequency and diversity, antibodies derived from NeoMab mice demonstrate affinity and functional activity comparable to, or even surpassing, FDA-approved drugs. In conclusion, the NeoMab mouse model in the BALB/c background has been rigorously validated to elicit a robust response to specific antigen immunization, producing antibodies with high affinity, diversity, and functional activity. GemPharmatech's extensive drug-target gene humanized mouse library (comprising over 800 targets) and diverse disease models in oncology and other fields facilitate a seamless connection between in vitro antibody screening and in vivo animal studies. The integration of NeoMab, target humanization animals, and disease models enables GemPharmatech to provide an integrated solution, reducing time and costs while elevating the quality of antibody discovery in the field. Citation Format: Mingkun Zhang, Cunxiang Ju, Song Li, Junchao Peng, Jing Zhao, Xiang Gao. NeoMab: A novel platform for fully human therapeutic antibody development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5333.