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uPAR-targeting cytotoxic antibody–drug conjugates selectively deplete proinflammatory myeloid cells for autoimmune indications

Xiang H, Mortenson GP, Lang SB, Jakkaraju S, Chirala A, Zhu Y, Jia M, Wen J, Chen Y, Baghela A, Chen YC, Sze MA, Hegde LG, Zhang-Hoover J, Willingham A, Handa M, Chi A, Baltus GA, Kamath RV, Levesque M, Vollmann EH (2026) uPAR-targeting cytotoxic antibody–drug conjugates selectively deplete proinflammatory myeloid cells for autoimmune indications. Cells 15(9):803. doi: 10.3390/cells15090803

Objective: To explore uPAR as a cell-surface marker to target and eliminate proinflammatory monocytes and macrophages using antibody–drug conjugates (ADCs).

Summary: Using recent scRNA-seq findings from RA patients, the authors identified the urokinase plasminogen activator receptor (uPAR), encoded by PLAUR, as a highly expressed cell surface marker on an inflammation-associated IL1B+ proinflammatory myeloid subset. an anti-uPAR mAb conjugated with monomethyl auristatin F (MMAF) was employed to demonstrate selective depletion of uPARhigh-expressing macrophages in a myeloid-rich rodent model.

Usage: Fab-ZAP rat (IT-55) was used to test the internalization capacity of anti-mouse uPAR mAbs. Saporin and Fab-IgG-ZAP were used as control.

Related Products: Fab-ZAP rat (Cat. #IT-55), Fab IgG-SAP (Cat. #IT-67), Saporin (Cat. #PR-01)

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