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

Elena J. Orlando, Xia Han, Catherine Tribouley, Patricia A. Wood, Rebecca J. Leary, Markus Riester, John E. Levine, Muna Qayed, Stephan A. Grupp, Michael Boyer, Barbara De Moerloose, Eneida R. Nemecek, Henrique Bittencourt, Hidefumi Hiramatsu, Jochen Buechner, Stella M. Davies, Michael R. Verneris, Kevin Nguyen, Jennifer L. Brogdon, Hans BitterMichael Morrissey, Piotr Pierog, Serafino Pantano, Jeffrey A. Engelman, Wendy Winckler

Research output: Contribution to journalArticle

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1504-1506
Number of pages3
JournalNature medicine
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2018

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Orlando, E. J., Han, X., Tribouley, C., Wood, P. A., Leary, R. J., Riester, M., Levine, J. E., Qayed, M., Grupp, S. A., Boyer, M., De Moerloose, B., Nemecek, E. R., Bittencourt, H., Hiramatsu, H., Buechner, J., Davies, S. M., Verneris, M. R., Nguyen, K., Brogdon, J. L., ... Winckler, W. (2018). Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nature medicine, 24(10), 1504-1506. https://doi.org/10.1038/s41591-018-0146-z