The Acquisition of Complement-Dependent Cytotoxicity by the Type II Anti-CD20 Therapeutic Antibody Obinutuzumab.

ABSTRACT: Rituximab, a prototypic anti-CD20 mAb, and the third-generation anti-CD20 mAb obinutuzumab differ in their ability to activate the complement system. According to recent studies, this contrast stems from the architecture of the antigen-antibody complex formed by these two mAbs that facilitates (rituximab) or disables (obinutuzumab) further oligomerization, leading to engagement of the initial classical complement pathway component C1q. We examined whether a gain-of-function C2 variant that acts downstream of C1q and enforces the formation of complement convertase resistant to physiological decay can impact complement activation by obinutuzumab. Co-application of the C2 variant with obinutuzumab and human serum resulted in complement-dependent cytotoxicity equal to or higher than attainable

SUBMITTER: Kuzniewska A 

PROVIDER: S-EPMC10778491 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature