{Reference Type}: Journal Article
{Title}: Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting.
{Author}: Schoenfeld K;Harwardt J;Habermann J;Elter A;Kolmar H;
{Journal}: Front Immunol
{Volume}: 14
{Issue}: 0
{Year}: 2023
{Factor}: 8.786
{DOI}: 10.3389/fimmu.2023.1258700
{Abstract}: 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.