Article
Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.
Nature medicine - 1 Oct 2018
Orlando Elena J, Han Xia, Tribouley Catherine, Wood Patricia A, Leary Rebecca J, Riester Markus, Levine John E, Qayed Muna, Grupp Stephan A, Boyer Michael, De Moerloose Barbara, Nemecek Eneida R, Bittencourt Henrique, Hiramatsu Hidefumi, Buechner Jochen, Davies Stella M, Verneris Michael R, Nguyen Kevin, Brogdon Jennifer L, Bitter Hans, Morrissey Michael, Pierog Piotr, Pantano Serafino, Engelman Jeffrey A, Winckler Wendy
Abstract excerpt
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...
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