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© Research
Publication : Science (New York, N.Y.)

Binding mechanisms of therapeutic antibodies to human CD20.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Science (New York, N.Y.) - 14 Aug 2020

Kumar A, Planchais C, Fronzes R, Mouquet H, Reyes N,

Link to Pubmed [PMID] – 32792392

Link to DOI [DOI] – 10.1126/science.abb8008

Science 2020 Aug; 369(6505): 793-799

Monoclonal antibodies (mAbs) targeting human antigen CD20 (cluster of differentiation 20) constitute important immunotherapies for the treatment of B cell malignancies and autoimmune diseases. Type I and II therapeutic mAbs differ in B cell binding properties and cytotoxic effects, reflecting differential interaction mechanisms with CD20. Here we present 3.7- to 4.7-angstrom cryo-electron microscopy structures of full-length CD20 in complexes with prototypical type I rituximab and ofatumumab and type II obinutuzumab. The structures and binding thermodynamics demonstrate that upon binding to CD20, type II mAbs form terminal complexes that preclude recruitment of additional mAbs and complement components, whereas type I complexes act as molecular seeds to increase mAb local concentration for efficient complement activation. Among type I mAbs, ofatumumab complexes display optimal geometry for complement recruitment. The uncovered mechanisms should aid rational design of next-generation immunotherapies targeting CD20.

https://pubmed.ncbi.nlm.nih.gov/32792392