CD40- and CD95-specific antibody single chain-Baff fusion proteins display BaffR-, TACI- and BCMA-restricted agonism.

ABSTRACT: Antibodies that target a clinically relevant group of receptors within the tumor necrosis factor receptor superfamily (TNFRSF), including CD40 and CD95 (Fas/Apo-1), also require binding to Fc gamma receptors (FcγRs) to elicit a strong agonistic activity. This FcγR dependency largely relies on the mere cellular anchoring through the antibody's Fc domain and does not involve the engagement of FcγR signaling. The aim of this study was to elicit agonistic activity from αCD40 and αCD95 antibodies in a myeloma cell anchoring-controlled FcγR-independent manner. For this purpose, various antibody variants (IgG1, IgG1_N297A, Fab₂) against the TNFRSF members CD40 and CD95 were genetically fused to a single-chain-encoded B-cell activating factor (scBaff) trimer as a C-terminal my

SUBMITTER: Nelke J 

PROVIDER: S-EPMC7531569 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature