Common light chain chickens produce human antibodies of high affinity and broad epitope coverage for the engineering of bispecifics.

ABSTRACT

Bispecific antibodies are an important and growing segment in antibody therapeutics, particularly in the immuno-oncology space. Manufacturing of a bispecific antibody with two different heavy chains is greatly simplified if the light chains can be the same for both arms of the antibody. Here, we introduce a strain of common light chain chickens, called OmniClic®, that produces antibody repertoires largely devoid of light chain diversity. The antibody repertoire in these chickens is composed of diverse human heavy chain variable regions capable of high-affinity antigen-specific binding and broad epitope diversity when paired with the germline human kappa light chain. OmniClic birds can be used in immunization campaigns for discovery of human heavy chains to different targets. Subsequent pairing of the heavy chain with a germline human kappa light chain serves to facilitate bispecific antibody production by increasing the efficiency of correct pairing. Abbreviations AID activation-induced cytidine deaminase; bsAb bispecific antibody; CDR complementarity-determining region; CL light chain constant region; CmLC common light chain; D diversity region; ELISA enzyme-linked immunosorbent assay; FACS fluorescence-activated cell sorting; Fc fragment crystallizable; FcRn neonatal Fc receptor; FR framework region; GEM gel-encapsulated microenvironment; Ig immunoglobulin; IMGT the international ImMunoGeneTics information system®; J joining region; KO knockout; mAb monoclonal antibody; NGS next-generation sequencing; PBS phosphate-buffered saline; PCR polymerase chain reaction; PGC primordial germ cell; PGRN progranulin; TCR T cell receptor; V variable region; VK kappa light chain variable region; VL light chain variable region; VH heavy chain variable region.