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

We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTLO19) 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 CTLO19.