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

Orlando, Elena J; Han, Xia; Tribouley, Catherine; Wood, Patricia A; Leary, Rebecca J; Riester, Markus; Levine, John E; Qayed, Muna et al. · Nat Med · 2018

basic_science · Level V

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Abstract

We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19<sup>-</sup> 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.

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