Polatuzumab vedotin

Polatuzumab vedotin is an antibody-drug conjugate consisting of a CD79b-directed antibody, a microtubule-disrupting agent called monomethyl auristatin E (MMAE), and a cleavable linker that holds the components together. CD79 is a heterodimer composed of CD79a and CD79b. Responsible for signal transduction, CD79 forms a complex with the B cell receptor (BCR) and is almost exclusively expressed on B cells, including malignant B cells. Most importantly, CD79b gained increasing attention as a promising therapeutic target as it plays an essential role in BCR expression, transport, and functions such as B cell proliferation and differentiation.

Once the antibody component binds to CD79b, polatuzumab vedotin is internalized, and lysosomal proteases cleave the linker to release MMAE in the cell. MMAE is a microtubule-disrupting anti-mitotic agent that exerts cytotoxic effects against malignant B cells. It binds to microtubules, inhibits mitosis by interfering with tubulin and tubulin polymerization, and induces apoptosis in dividing B cells.