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Industry’s Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy

  • Stacie IttershagenEmail author
  • Solveig Ericson
  • Lamis Eldjerou
  • Ali Shojaee
  • Eric Bleickardt
  • Manisha Patel
  • Tetiana Taran
  • Oezlem Anak
  • Charlene Hall
  • Mimi Leung
  • Deborah Roccoberton
  • Florence Salmon
  • Miriam Fuchs
  • Vadim Romanov
  • David Lebwohl
Stem Cell Transplantation (R Maziarz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Stem Cell Transplantation

Abstract

Purpose of Review

We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children’s Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland).

Recent Findings

Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma. Subsequent approvals in the European Union, Switzerland, and Canada soon followed.

Summary

The tisagenlecleucel success story represents the development and commercialization of a first-of-its-kind personalized cellular therapy with a manufacturing process that supports commercial production and ongoing global clinical trials in a growing number of countries.

Keywords

Acute lymphoblastic leukemia (ALL) Chimeric antigen receptor (CAR) Chimeric antigen receptor T cell (CAR-T) Chronic lymphoblastic leukemia (CLL) Tisagenlecleucel Diffuse large B cell lymphoma (DLBCL) 

Notes

Acknowledgments

The authors would like to thank the following institutions and people for their valuable contributions to the development of the Novartis CAR-T cell program: The University of Pennsylvania, The Children’s Hospital of Philadelphia, clinical trial investigators, patients and families, Herve Hoppenot, Manuel Lichtman, David Epstein, Samuele Butera, Pascal Touchon, Serge Runser, Margit Jeschke, Karen Thudium, Jens Hasskarl, Patricia Wood, Ewelina Morawa, Lida Pacaud, Chris Keir, Spencer Fisk, Carl June, Stephan Grupp, Shannon Maude, Stephen Schuster, David Porter, David Teachey, Bruce Levine, William Chou, Stefanie Possekel, Mark Fishman, Bill Sellers, Allessandro Riva, Joe Jimenez, Juan Andres, Richard Tarapata, Michael Christiano, Nancy Griffin, Chris Klee, Chuck Wilson, Jennifer Brogdon, Abhijit Agarwal, Matthew Robson, Yanni Hao, Yan Lui, Jie Zhang, Kristen Harrington-Smith, Julie Millon, Karen Russo, Elaine Harney, Beth Ostergaard-Stillwell, Mark Morton, Clifford Baum, Sweta Shah, Kathryn Lund, Angela Shen, Marty Giedlin, Andrew Trovato, Kathrin Jinivizian, Charlene Hall, Lisa Haystrand, Rachelle Senzon, Maanasa Gowda, Lan Cao, Jason Hamilton, Narin Ahmed, Viera Muzithras, Nandita Shangari, Lori Tomassian.

Editorial assistance was provided Michael Hobert, PhD, of ProEd Communications, Inc., and was supported by Novartis Pharmaceuticals Corporation.

Funding

Editorial assistance was supported by Novartis Pharmaceuticals Corporation.

Compliance with Ethical Standards

Conflict of Interest

Stacie Ittershagen, Lamis Eldjerou, Eric Bleickardt, Manisha Patel, Oezlem Anak, Charlene Hall, Mimi Leung, Ali Shojaee, Deborah Roccoberton, Miriam Fuchs, and Florence Salmon declare that they are employees of Novartis Pharmaceuticals Corporation.

Solveig Ericson, Tetiana Taran, Vadim Romanov, and David Lebwohl declare that they are employees and shareholders of Novartis Pharmaceuticals Corporation.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Supplementary material

11899_2019_498_MOESM1_ESM.docx (24 kb)
ESM 1 (DOCX 24 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Stacie Ittershagen
    • 1
    Email author
  • Solveig Ericson
    • 1
  • Lamis Eldjerou
    • 1
  • Ali Shojaee
    • 1
  • Eric Bleickardt
    • 1
  • Manisha Patel
    • 1
  • Tetiana Taran
    • 1
  • Oezlem Anak
    • 2
  • Charlene Hall
    • 1
  • Mimi Leung
    • 1
  • Deborah Roccoberton
    • 1
  • Florence Salmon
    • 2
  • Miriam Fuchs
    • 2
  • Vadim Romanov
    • 1
  • David Lebwohl
    • 1
  1. 1.Novartis Pharmaceuticals CorporationEast HanoverUSA
  2. 2.Novartis Pharma AGBaselSwitzerland

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