Anti-CD37 antibody-drug conjugate IMGN529

anti-CD37 antibody-drug conjugate IMGN529

An immunoconjugate that consists of a humanized IgG1 antibody K7153A against the cell-surface antigen CD37.

Chemistry

It is covalently linked via the uncleavable, maleimide-derived thioether-based linker SMCC to the maytansinoid DM1.

Pro-apoptotic and cytotoxic activity

It has potential pro-apoptotic and cytotoxic activities.

Cell mediated cytotoxicity

The antibody moiety of IMGN529 binds to CD37 on tumor B cells and induces an antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), thereby showing pro-apoptotic activity.

Effect on Tubulin polymerization

• In addition, after the internalization of this agent and lysosomal degradation, the DM1 moiety binds to tubulin and inhibits tubulin polymerization and microtubule assembly.
• This in turn results in a disruption of microtubule activity and cell division, and eventually causing cell death in CD37-positive B cells.

Overexpression of CD37 in malignancies

CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies.

Stability

Compared to reducible, cleavable linkers, the non-reducible SMCC linker shows increased stability in plasma.

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