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

Ruella M1,2,3,4,5, Xu J1,2,3, Barrett DM6, Fraietta JA1,2,3,4, Reich TJ1, Ambrose DE1, Klichinsky M1,7, Shestova O1, Patel PR1, Kulikovskaya I1, Nazimuddin F1, Bhoj VG1,2,3, Orlando EJ8, Fry TJ9, Bitter H8, Maude SL6, Levine BL1,2,3, Nobles CL10, Bushman FD10, Young RM1, Scholler J1, Gill SI1,3,5, June CH11,12,13,14, Grupp SA6, Lacey SF1,2,3, Melenhorst JJ15,16,17. 1Center 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