Sean R Corcoran, James D Phelan, Jaewoo Choi, Galina Shevchenko, Rachel E Fenner, Xin Yu, Sebastian Scheich, Tony Hsiao, Vivian M Morris, Evangelia K Papachristou, Kamal Kishore, Clive S D'Santos, Yanlong Ji, Stefania Pittaluga, George W Wright, Henning Urlaub, Kuan-Ting Pan, Thomas Oellerich, Jagan Muppidi, Daniel J Hodson, Louis M Staudt
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 determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity...
April 25, 2024: Cancer Discovery