Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Jonathan P Mochel
* ORCID logo ,
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
Version 1 : Received: 19 November 2018 / Approved: 21 November 2018 / Online: 21 November 2018 (11:34:58 CET)

A peer-reviewed article of this Preprint also exists.

Mochel, J.P., Ekker, S.C., Johannes, C.M., Jergens, A.E., Allenspach, K., Bourgois-Mochel, A., Knouse, M., Benzekry, S., Wierson, W., LeBlanc, A.K. and Kenderian, S.S., 2019. CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies. The AAPS journal, 21(3), p.50. Mochel, J.P., Ekker, S.C., Johannes, C.M., Jergens, A.E., Allenspach, K., Bourgois-Mochel, A., Knouse, M., Benzekry, S., Wierson, W., LeBlanc, A.K. and Kenderian, S.S., 2019. CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies. The AAPS journal, 21(3), p.50.

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 U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), 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.

Keywords

immuno-oncology; CAR T-cell; lymphoma; one health

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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