Abstract 13P
Background
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 (ICIs).
Methods
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.
Results
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 labor 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.
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.