Effector-attenuating Substitutions That Maintain Antibody Stability and Reduce Toxicity in Mice.

ABSTRACT: The antibody Fc region regulates antibody cytotoxic activities and serum half-life. In a therapeutic context, however, the cytotoxic effector function of an antibody is often not desirable and can create safety liabilities by activating native host immune defenses against cells expressing the receptor antigens. Several amino acid changes in the Fc region have been reported to silence or reduce the effector function of antibodies. These earlier studies focused primarily on the interaction of human antibodies with human Fc-γ receptors, and it remains largely unknown how such changes to Fc might translate to the context of a murine antibody. We demonstrate that the commonly used N297G (NG) and D265A, N297G (DANG) variants that are efficacious in attenuating effector function in primates retai

SUBMITTER: Lo M 

PROVIDER: S-EPMC5339770 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature