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

By M. Ruella, Jun Xu, David M. Barrett, J. Fraietta, Tyler J. Reich, David E. Ambrose, M. Klichinsky, O. Shestova, Prachi R Patel, I. Kulikovskaya and 16 more. Nature Medicine, 2018

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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. A CAR gene unintentionally introduced in a contaminating leukemia cell during the manufacturing of CAR T cells caused a patient to relapse after therapy.

Subfields: Genetics, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/86af65a42de9ada1b07c0d89042e12f9269468fb

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Citations in the corpus

• Engineering strategies to overcome the current roadblocks in CAR T cell therapy (2019, background): “…harvested together with lymphocytes in the apheresis product can inadvertently be transduced with the CAR construct, which can result in antigen masking via binding of CARs expressed by these tumour cells to TAA on the same cells, resulting in clonal expansion and tumour cell escape in vivo 249 .”