High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources.

摘要: Interest in single-domain antibodies (sdAbs) stems from their unique structural/pronounced, hence therapeutically desirable, features. From the outset-as therapeutic modalities-human antibody heavy chain variable domains (VHs) attracted a particular attention compared with 'naturally-occurring' camelid and shark heavy-chain-only (VHHs VNARs, respectively) due to perceived lack of immunogenicity. However, they have not quite lived up initial promise as VH hits, primarily mined synthetic phage display libraries, too often been plagued aggregation tendencies, low solubility affinity. Largely unexplored, camelized human libraries appeared remediated problem, but affinity hits still persisted, requiring undertaking additional, laborious maturation steps render VHs feasible. A wholesome resolution has recently emerged development non-canonical transgenic rodent discovery platforms that appear facilely profusely generate high affinity, aggregation-resistant VHs.