Regeneron Pharmaceuticals, Inc.
GENETICALLY MODIFIED NON-HUMAN ANIMALS FOR GENERATING THERAPEUTIC ANTIBODIES AGAINST PEPTIDE-MHC COMPLEXES, METHODS OF MAKING AND USES THEREOF

Abstract:

A non-human animal is genetically modified with sequence encoding a human or humanized MHC molecule or associated molecule, e.g., .beta.2 microglobulin, and expression of the sequence by the non-human animal induces tolerance to the corresponding human HLA from which the human or human MHC molecule is derived. The tolerance exhibited by these non-human animals allows these animals to generate specific antibody responses to the corresponding human HLA when such HLA is presenting a peptide that is antigenic to the non-human animal. Such an antibody response, which specifically targets a pMHC complex of interest without binding to the MHC molecule may be useful in immunotherapeutic modalities that target a component of the immunological synapse which provides the specificity of that interaction.