Project description:Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify molecular determinants of sensitivity to Pola-V, we used CRISPR-Cas9 screening for genes that modulated the toxicity of Pola-V for lymphomas or the surface expression of its target, CD79B. Our results reveal a striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity. Genetic, pharmacological, and enzymatic approaches that remove terminal sialic acid residues from N-linked glycans enhanced lymphoma killing by Pola-V. Pola-V toxicity was also modulated by KLHL6, a ubiquitin ligase that targets CD79B for degradation in normal and malignant germinal center B cells, explaining its recurrent inactivation in germinal center-derived lymphomas. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.

2024-07-12 | PXD043670 | Pride

Cost-effectiveness of polatuzumab vedotin plus chemoimmunotherapy for untreated diffuse large B-cell lymphoma in China

Project description: Not available

| S-EPMC12350607 | biostudies-literature

The molecular rationale for the combination of polatuzumab vedotin plus rituximab in diffuse large B-cell lymphoma.

Project description: Not available

| S-EPMC9796291 | biostudies-literature

Polatuzumab vedotin and CD79B: A study of efficacy in R-CHOP-resistant diffuse large B-cell lymphoma.

Project description: Not available

| S-EPMC12710110 | biostudies-literature