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Genetically modified non-human animals for generating therapeutic antibodies against peptide-MHC complexes, methods of making and uses thereof
Genetically modified non-human animals for generating therapeutic antibodies against peptide-MHC complexes, methods of making and uses thereof
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机译:用于产生针对肽-MHC复合物的治疗性抗体的转基因非人类动物,其制备方法和用途
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摘要
A non-human animal is genetically modified with sequence encoding a human or humanized MHC molecule or associated molecule, e.g., β2 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.
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