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The AAPS Journal

, 21:50 | Cite as

CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies

  • Jonathan P. MochelEmail author
  • Stephen C. Ekker
  • Chad M. Johannes
  • Albert E. Jergens
  • Karin Allenspach
  • Agnes Bourgois-Mochel
  • Michael Knouse
  • Sebastien Benzekry
  • Wesley Wierson
  • Amy K. LeBlanc
  • Saad S. Kenderian
Commentary Theme: Precision Medicine: Implications for the Pharmaceutical Sciences
Part of the following topical collections:
  1. Theme: Precision Medicine: Implications for the Pharmaceutical Sciences

Abstract

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20–100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This commentary summarizes the current state of knowledge on CAR T cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

Key Words

ommuno-oncology CAR T cell lymphoma One Health 

Notes

Author Contributions

All authors (JPM, SE, CJ, AJ, KA, ABM, MK, SB WW, AKL, SSK) have contributed to the writing of the manuscript. JPM was responsible for the final production of the commentary. All authors have read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of Interest

JPM, SE, CJ, AJ, KA, WW, and SSK are founders of LifEngine Animal Health Laboratories, Inc. SSK is inventor on patents in the CAR T cell therapy field that are licensed to Novartis. This work was partially supported (AKL) by the Intramural Program of the National Cancer Institute, NIH (Z01-BC006161).

Disclaimer

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Jonathan P. Mochel
    • 1
    • 2
    Email author
  • Stephen C. Ekker
    • 3
  • Chad M. Johannes
    • 4
  • Albert E. Jergens
    • 4
  • Karin Allenspach
    • 4
  • Agnes Bourgois-Mochel
    • 4
  • Michael Knouse
    • 1
  • Sebastien Benzekry
    • 5
  • Wesley Wierson
    • 6
  • Amy K. LeBlanc
    • 7
  • Saad S. Kenderian
    • 8
    • 9
  1. 1.Department of Biomedical SciencesIowa State UniversityAmesUSA
  2. 2.Iowa State University College of Vet. MedicineAmesUSA
  3. 3.Mayo Clinic Cancer Center Department of Biochemistry and Molecular BiologyRochesterUSA
  4. 4.Department of Veterinary Clinical SciencesIowa State UniversityAmesUSA
  5. 5.Team MONCInstitut National de Recherche en Informatique et en AutomatiqueBordeauxFrance
  6. 6.Department of Genetics, Development, and Cell BiologyIowa State UniversityAmesUSA
  7. 7.Comparative Oncology ProgramCenter for Cancer Research National Cancer InstituteBethesdaUSA
  8. 8.Department of MedicineMayo Clinic Division of HematologyRochesterUSA
  9. 9.Department of ImmunologyMayo ClinicRochesterUSA

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