Abstract 3435: B cell TuLibs: Immortalized tumor-derived B cell libraries for the interrogation and unbiased discovery of novel therapeutic targets and antibodies from patients

Abstract The use of B cell repertoires for antigen and antibody discovery is on the rise due to the emergence of new techniques to tap into the human antigen-experienced B cell repertoire. Recently, many research groups have shown that the presence of tumor-infiltrating B cells or Tertiary Lymphoid Structures (TLS) at tumor sites correlate with improved survival and response to Immune Checkpoint Inhibitors. Here, we present Kling Biotherapeutic’s platform that enables the discovery of novel therapeutic targets and antibody-pairs. We overcome the limited proliferative lifespan of primary human and animal B cells by transduction with a proprietary vector to express Bcl6 and Bcl-xL, which prevents both terminal differentiation and apoptosis. Through the highly efficient isolation and immortalization of tumor- or TLS-derived B cells, our approach captures the B cell diversity and all Ig-isotypes from all tissues. As opposed to the labour intensive and costly approach of ex vivo BCR sequencing and subsequent recombinant antibody production and validation, our B-cell Tumor Libraries (TuLibs) secrete antibodies into the culture supernatant while retaining indefinite expansion capabilities, allowing for immediate functional screening of antibodies and rapid identification of unique tumor-specific B cell clones. Moreover, our immortalized B cells retain the ability to undergo somatic-hypermutation, allowing for in vitro affinity maturation of immortalized B cell clones against targets of interest. Altogether, Kling Biotherapeutic’s proprietary platform allows the comprehensive functional screening and affinity maturation of human and animal B cell repertoires from multiple tissues sources. TuLibs represents a significant advancement in our ability to identify new immuno-functional targets and antibodies for biopharmaceutical development of tumor targeted therapies. Citation Format: Casper Marsman, Jurgen Heinen, Kelly Maijoor, Arjen Bakker, Rob Roovers, Michael Koslowski, Stefano Gulla, Alessandra Micaela Villa. B cell TuLibs: Immortalized tumor-derived B cell libraries for the interrogation and unbiased discovery of novel therapeutic targets and antibodies from patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3435.