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Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Orlando, Elena and Han, Xia and Wood, Patricia and Leary, Rebecca and Pierog, Peter and Brogdon, Jennifer and Bitter, Hans and Morrissey, Michael and Pantano, Serafino and Adamovich, Wendy and Tribouley, Catherine and Kevin, Nguyen and John, Levine and Muna, Qayad and Stephan, Grupp and Michael, Boyer and Barbara, DeMoerloose and Eneida, Nemecek and Henrique, Bittencourt and Hidefumi, Hiramatsu and Jochen, Büchner and Stella, Davies and Michael, Verneris and Engelman, Jeffrey (2018) Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nature Medicine, 24. pp. 1504-1506. ISSN 1546170X

Abstract

We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19– relapse to chimeric antigen receptor (CAR) therapy. The mutations are present in the vast majority of resistant tumor cells and are predicted to lead to a truncated protein with a nonfunctional or absent transmembrane domain and consequently to a loss of surface antigen. This irreversible loss of CD19 advocates for an alternative targeting or combination CAR approach.

Item Type: Article
Date Deposited: 19 Dec 2018 00:45
Last Modified: 19 Dec 2018 00:45
URI: https://oak.novartis.com/id/eprint/35377

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