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

  • Commentary
  • Theme: Precision Medicine: Implications for the Pharmaceutical Sciences
  • Published:
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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.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Iowa State University, Ames, Iowa, 50011, USA

    Jonathan P. Mochel & Michael Knouse

  2. Iowa State University College of Vet. Medicine, 2448 Lloyd, 1809 S Riverside Dr., Ames, Iowa, 50011-1250, USA

    Jonathan P. Mochel

  3. Mayo Clinic Cancer Center Department of Biochemistry and Molecular Biology, Rochester, Minnesota, 55905, USA

    Stephen C. Ekker

  4. Department of Veterinary Clinical Sciences, Iowa State University, Ames, Iowa, 50011, USA

    Chad M. Johannes, Albert E. Jergens, Karin Allenspach & Agnes Bourgois-Mochel

  5. Team MONC, Institut National de Recherche en Informatique et en Automatique, Bordeaux, France

    Sebastien Benzekry

  6. Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, Iowa, 50011, USA

    Wesley Wierson

  7. Comparative Oncology Program, Center for Cancer Research National Cancer Institute, Bethesda, Maryland, 20892, USA

    Amy K. LeBlanc

  8. Department of Medicine, Mayo Clinic Division of Hematology, Rochester, Minnesota, 55905, USA

    Saad S. Kenderian

  9. Department of Immunology, Mayo Clinic, Rochester, Minnesota, 55905, USA

    Saad S. Kenderian

Authors
  1. Jonathan P. Mochel
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  2. Stephen C. Ekker
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  3. Chad M. Johannes
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  4. Albert E. Jergens
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  5. Karin Allenspach
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  6. Agnes Bourgois-Mochel
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  7. Michael Knouse
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  8. Sebastien Benzekry
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  9. Wesley Wierson
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  10. Amy K. LeBlanc
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  11. Saad S. Kenderian
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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.

Corresponding author

Correspondence to Jonathan P. Mochel.

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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).

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Mochel, J.P., Ekker, S.C., Johannes, C.M. et al. CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies. AAPS J 21, 50 (2019). https://doi.org/10.1208/s12248-019-0322-1

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  • DOI: https://doi.org/10.1208/s12248-019-0322-1

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