Lelieveldt L (2019) Chemical strategies for antigen-selective targeting of autoreactive B Cells. Chapter 2: Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Radboud Universiteit Nijmegen Nijmegen, Netherlands 45-64. Thesis.
Objective: To develop a method to target and selectively eliminate autoreactive B cells that produce anti-citrullinated proteins antibodies (ACPA) using a sequential antigen prodrug targeting strategy, as a treatment for Rheumatoid Arthritis (RA).
Summary: The study used a synthesized cyclic citrullinated peptide (CCP) antigen suitable for BCR binding and demonstrated that binding by ACPA was impaired upon introduction of a carboxy-pnitrobenzyl (CNBz) caging group at the side chain of the citrulline residue. Enzymatic reduction of the CNBz moiety by nitroreductase fully restored citrulline-selective recognition by both ACPA and ACPA-expressing B cells and showed targeted cell death of CCP-recognizing B cells only. These results mark an important step towards antigen-selective B cell targeting in general and more specifically in RA.
Usage: Streptavidin-ZAP mixed with biotinylated CCP peptides was tested in cytotoxicity assays. The exposure of cells to CCP-SA-ZAP at 1 nM as well as the activated CCP(CNBz) induced death of up to 60% of ACPA-expressing B cells.
Related Products: Streptavidin-ZAP (Cat. #IT-27)