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Acknowledgements

We thank the patients for their participation in the clinical trials from which research samples were obtained. We also acknowledge A. Fesnak, A. Lamontagne, A. Malykhin, C. Corl, Y. Ohayon and other members of the Clinical Cell and Vaccine Production Facility for cell manufacturing and testing. In addition, we are grateful to V. Gonzalez, J. Finklestein, F. Nazimuddin, J.-M. Navenot, M. Bogush, Y. Tanner, N. Kengle, K. Marcucci, A. Chew, C. Pletcher, P. Hallberg and R. Schretzenmair for contributions to correlative studies and/or other research support. D. Campana, C. Imai and others at St. Jude Children’s Research Hospital designed, developed and provided, under material-transfer agreements, the CAR used in this study. B. Jena and L. Cooper (MD Anderson Cancer Center) are acknowledged for providing the CAR anti-idiotype detection reagent. The functional anti-idiotypic antibody that was used for in vitro CAR stimulation experiments was a kind gift from Novartis Pharmaceutical Corporation. This work was supported by funding from NCI T32CA009140 (J.A.F.) R01CA165206 (D.L.P. and C.H.J.), P01CA214278 (C.H.J), a Stand Up to Cancer Phillip A. Sharp Innovation in Collaboration Award (C.H.J) and Novartis.

Author information

Author notes

  1. These authors contributed equally: Simon F. Lacey and Elena J. Orlando.

Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Joseph A. Fraietta
    • , Simon F. Lacey
    • , F. Brad Johnson
    • , Megan M. Davis
    • , Bruce L. Levine
    • , Donald L. Siegel
    • , David L. Porter
    • , Carl H. June
    •  & J. Joseph Melenhorst
  2. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA

    • Joseph A. Fraietta
    • , Simon F. Lacey
    • , Mercy Gohil
    • , Stefan Lundh
    • , Alina C. Boesteanu
    • , Yan Wang
    • , Roddy S. O’Connor
    • , Edward Pequignot
    • , David E. Ambrose
    • , Changfeng Zhang
    • , Nicholas Wilcox
    • , Felipe Bedoya
    • , Corin Dorfmeier
    • , Fang Chen
    • , Lifeng Tian
    • , Harit Parakandi
    • , Minnal Gupta
    • , Regina M. Young
    • , Irina Kulikovskaya
    • , Li Liu
    • , Jun Xu
    • , Megan M. Davis
    • , Bruce L. Levine
    • , Noelle V. Frey
    • , Donald L. Siegel
    • , Carl H. June
    •  & J. Joseph Melenhorst
  3. Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA

    • Joseph A. Fraietta
    • , Simon F. Lacey
    • , Alexander C. Huang
    • , E. John Wherry
    • , Carl H. June
    •  & J. Joseph Melenhorst
  4. Novartis Institutes for BioMedical Research, Cambridge, MA, USA

    • Elena J. Orlando
    • , Iulian Pruteanu-Malinici
    • , Sadik H. Kassim
    • , Hans Bitter
    •  & Jennifer L. Brogdon
  5. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    • Wei-Ting Hwang
  6. Division of Hematology-Oncology, Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Noelle V. Frey
    •  & David L. Porter
  7. Division of Transfusion Medicine and Therapeutic Pathology, University of Pennsylvania, Philadelphia, PA, USA

    • Donald L. Siegel
  8. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Alexander C. Huang
    •  & E. John Wherry

Contributions

J.A.F., S.F.L., F.B.J., R.M.Y., N.V.F., B.L.L., D.L.S., E.J.W., J.L.B., D.L.P., C.H.J. and J.J.M. designed the experiments and/or performed analysis. J.A.F., M.Gohil, S.L., A.C.B., Y.W., R.S.O., D.E.A., C.Z., N.W., F.B., C.D., F.C., L.T., H.P., M. Gupta, I.K., L.L., J.X., S.H.K., M.M.D. and A.C.H. performed experiments. E.J.O. and H.B. analyzed RNA-seq. data. I.P.-M. carried out the computational analyses of flow cytometric data. W.-T.H. and E.P. performed statistical analyses. J.A.F., C.H.J. and J.J.M. wrote the paper, and all authors contributed to writing and providing feedback.

Competing interests

J.A.F., S.F.L., F.B., R.M.Y., B.L.L., J.L.B., D.L.P., C.H.J. and J.J.M. hold patents related to CTL019 cell therapy. These authors declare no additional interests. The remaining authors declare no competing interests.

Corresponding author

Correspondence to J. Joseph Melenhorst.