Rationally Engineered Therapeutic Proteins with Reduced Immunogenicity
作者： Shabnam Tangri , Bianca R. Mothé , Julie Eisenbraun , John Sidney , Scott Southwood
DOI: 10.4049/JIMMUNOL.174.6.3187
关键词:
摘要: Chronic administration of protein therapeutics may elicit unacceptable immune responses to the specific protein. Our hypothesis is that immunogenicity drugs can be ascribed a few immunodominant helper T lymphocyte (HTL) epitopes, and reducing MHC binding affinity these HTL epitopes contained within proteins generate with lower immunogenicity. To test this hypothesis, we studied therapeutic erythropoietin (Epo). Two regions Epo, designated Epo 91-120 126-155, were recognized by individuals numerous HLA-DR types, property common epitopes. We then engineered analog reduced HLA affinity. These associated in vitro modified forms containing substitutions shown bioactive nonimmunogenic vitro. findings support our demonstrate systematic predictable manner.
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