DE-ADCC/CDC FUNCTIONS OF ANTIBODIES AND THEIR APPLICATIONS

摘要

The present invention provides De-ADCC/CDC activity monoclonal antibodies and their generation method and applications. The present invention modified the antibody sequences of multi-target sites such as PD-L1, PD-1, CTLA4, TNF-α, PCSK9, NGF, CD47 and C5. A flexible amino acid sequence was inserted between the heavy chain CDR3 and CH2 regions of IgG1 antibody to block the physical stress signal transmit from antigen-bound Fab to its Fc region to reduce the ADCC/CDC activity while not significantly increasing the formation of the polymers. The modified antibodies in the present invention and the original antibodies target the same sites, but the antibody subtype or glycosylation state is different. For the modified antibodies in the present invention, the stability is significantly improved or/and immunogenicity is significantly reduced, and the half-life is prolonged. The modified antibodies eliminate the activity of ADCC/CDC. Therefore, the antibody modified by the technology of the present invention can effectively avoid side effects caused by the activation of ADCC/CDC and other Fc-mediated functions and improve the curative effect of antibody drugs. It has excellent clinical application value and is suitable for promotion.