Generation of binder-format-payload conjugate-matrices by antibody chain-exchange

Generation of binder-format-payload conjugate-matrices by antibody chain-exchange

Blog Article

Abstract The generation of antibody-drug conjugates with optimal functionality depends on many parameters.These include binder epitope, antibody format, linker composition, conjugation site(s), drug-to-antibody ratio, L-Leucine and conjugation method.The production of matrices that cover all possible parameters is a major challenge in identifying optimal antibody-drug conjugates.

To address this bottleneck, we adapted our Format Chain Exchange technology (FORCE), originally established for bispecific antibodies, toward the generation of binder-format-payload matrices (pair-FORCE).Antibody derivatives with exchange-enabled Fc-heterodimers are combined with payload-conjugated Fc donors, and subsequent chain-exchange transfers payloads to antibody derivatives in different formats.The resulting binder-format-conjugate matrices can be generated with cytotoxic payloads, dyes, haptens, and large molecules, resulting in versatile tools for ADC screening campaigns.

We Carbon Film show the relevance of pair-FORCE for identifying optimal HER2-targeting antibody-drug conjugates.Analysis of this matrix reveals that the notion of format-defines-function applies not only to bispecific antibodies, but also to antibody-drug conjugates.