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

Bitter, Hans and Orlando, Elena and Marco, Ruella and Jun, Xu and David, Barrett and Joseph, Fraietta and Tyler , Reich and David , Ambrose and Michael, Klichinsky and Olga, Shestova and Prachi, Patel and Irina, Kulikovskaya and Farzana, Nazimuddin and Vijay, Bhoj and Shannon, Maude and Bruce, Levine and Christopher, Nobles and Frederic, Bushman and Regina, Young and John, Scholler and Saar, Gill and Carl, June and Stephan, Grupp and 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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