Abstract 14P
Background
Use of human B cells 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.
Methods
Here, we describe a proprietary platform named Kling-Select that enables the discovery of novel therapeutic target- and antibody-pairs by functional screening of the B cell repertoire of exceptional responders. We overcome the limited proliferative lifespan of primary human B cells by transduction with a proprietary vector to express Bcl6 and Bcl-xL. This effectively prevents both terminal differentiation and apoptosis resulting in permanently immortalized B cells. Kling-Select B cells are amenable to high-throughput processing through indefinite expansion capabilities, expression of the cognate B cell receptor on the cell surface and concomitant secretion of antibodies. The Kling-Select platform is exceptionally efficient, allowing for >85% immortalization of isolated antigen-experienced B cells. PBMC-derived B cells, tissue- or tumor-derived B cells are easily applied in the Kling-Select platform. This allows for novel target discovery by interrogation of tertiary lymphoid structures and tumor-infiltrating B cells. Finally, the Kling-Evolve platform allows for the in vitro maturation of B cell clones against targets of interest. This powerful technology can be used for the rapid evolution of neutralizing antibodies against emerging viral variants or for affinity and selectivity improvement of oncology assets.
Results
Recently, the EMA granted market approval for the respiratory syncytial virus (RSV) targeting monoclonal antibody Ab Nirsevimab (Beyfortus®) that was discovered using the Kling-Select platform. Nirsevimab arrests the RSV fusion protein in its prefusion state and is superior to the current standard of care.
Conclusions
Here we will discuss the application of Kling-Select and Kling-Evolve for the discovery of novel cancer targets and their corresponding human antibodies currently in clinical and preclinical development.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Marsman, J. Heinen, K. Maijoor, M. Kedde, R. Schotte, A. Bakker: Financial Interests, Personal, Stocks/Shares: Kling Biotherapeutics. M. Koslowski, S. Gullà: Financial Interests, Personal, Other: Kling Biotherapeutics.