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Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell

Bitter, Hans, Orlando, Elena, Marco, Ruella, Jun, Xu, David, Barrett, Joseph, Fraietta, Tyler , Reich, David , Ambrose, Michael, Klichinsky, Olga, Shestova, Prachi, Patel, Irina, Kulikovskaya, Farzana, Nazimuddin, Vijay, Bhoj, Shannon, Maude, Bruce, Levine, Christopher, Nobles, Frederic, Bushman, Regina, Young, John, Scholler, Saar, Gill, Carl, June, Stephan, Grupp, Joseph, Melenhorst and Simon, Lacey (2018) Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nature Medicine, 24 (10). pp. 1499-1503. ISSN 1546170X

Abstract

We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19– leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.

Item Type: Article
Date Deposited: 20 Nov 2018 00:45
Last Modified: 20 Nov 2018 00:45
URI: https://oak.novartis.com/id/eprint/35846

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