%0 Journal Article
%T Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting.
%A Schoenfeld K
%A Harwardt J
%A Habermann J
%A Elter A
%A Kolmar H
%J Front Immunol
%V 14
%N 0
%D 2023
%M 37841262
%F 8.786
%R 10.3389/fimmu.2023.1258700
%X Cancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain. Antibody masking impaired interaction with soluble pentameric as well as cell surface-expressed IgM molecules rendering the antibody cytotoxically inactive. Binding capacity of the anti-IgM antibody drug conjugate was restored upon conditional protease-mediated demasking which consequently enabled target-dependent antibody internalization and subsequent induction of apoptosis in malignant B cells. This easily adaptable approach potentially provides a novel mechanism of clonal B cell lymphoma eradication to the arsenal available for non-Hodgkin's lymphoma treatment.