Platform Approach For Identifying The Most Functional And Developable Bispecific T-Cell Engager

By Tom Cornell, Tim Wood, Dawn Bembridge, Chris Sayer, Evert Bokma, Patrick Lynch, Galia Konfortova, Cherry Chui, Mariarosaria Cerchia, Farnoush Masoudzadeh, Katie Welch, Erika Kovacs, Arron Hearn, Rob Holgate, and Campbell Bunce (Abzena, Babraham Research Campus, Cambridge, UK)

Designing bispecific antibodies is complex and presents significant challenges due to the intricacies involved in their formation and functionality. Various advanced technologies have been developed to assist in creating these sophisticated molecules, specifically targeting the heterodimerization of both heavy and light chains to ensure the proper structure and function of the antibodies. For instance, the "Knob-into-hole" technology facilitates the heavy chain heterodimerization process, while other methods, such as CrossMAb and single-chain variable fragments (scFvs) reformatting, are utilized for light chain pairing. Beyond these pairing strategies, other key considerations include the spatial proximity and arrangement of the bispecific antibody's functional arms, as well as the stoichiometry (e.g., 1:1, 2:1, 2:2) needed to achieve the optimal therapeutic effect.

This study specifically aims to assess a platform that supports the rational design and selection of bispecific antibodies to maximize their clinical efficacy. Two functionalities were evaluated in this context: one targeting cancer cells through anti-CD19 and the other recruiting T cells via anti-CD3, both crucial for enhancing immune response against cancer.