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Nat Med. 2018 Oct;24(10):1499-1503. doi: 10.1038/s41591-018-0201-9. Epub 2018 Oct 1.

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

Author information

1
Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
3
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
4
Parker Institute for Cellular Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA.
5
Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
6
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
7
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
8
Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
9
University of Colorado, Children's Hospital Colorado, Denver, CO, USA.
10
Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
11
Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.
12
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.
13
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.
14
Parker Institute for Cellular Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA. cjune@upenn.edu.
15
Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. mej@upenn.edu.
16
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. mej@upenn.edu.
17
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. mej@upenn.edu.

Abstract

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.

PMID:
30275568
DOI:
10.1038/s41591-018-0201-9

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