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Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell.

Marco Ruella, Jun Xu, David M Barrett, Joseph A Fraietta, Tyler J Reich, David E Ambrose, Michael Klichinsky, Olga Shestova, Prachi R Patel, Irina Kulikovskaya, Farzana Nazimuddin, Vijay G Bhoj, Elena J Orlando, Terry J Fry, Hans Bitter, Shannon L Maude, Bruce L Levine, Christopher L Nobles, Frederic D Bushman, Regina M Young, John Scholler, Saar I Gill, Carl H June, Stephan A Grupp, Simon F Lacey, J Joseph Melenhorst
Nature Medicine 2018 October
We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.

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