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

Nat Med 2018 10 1;24(10):1504-1506. Epub 2018 Oct 1.

Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

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.

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http://www.nature.com/articles/s41591-018-0146-z
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http://dx.doi.org/10.1038/s41591-018-0146-zDOI Listing
October 2018
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