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

The advent of the genome editing era brings forth the promise of adoptive cell transfer usingengineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cellimmunotherapy is probably one of the most encouraging developments for the treatment ofhematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food andDrug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the otherfor adult patients with advanced lymphomas. However, despite significant progress in the area, CART-cell therapy is still in its early days and faces significant challenges, including the complexity andcosts associated with the technology. B-cell lymphoma is the most common hematopoietic cancer indogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is awidely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment iswith combination chemotherapy protocols, which prolong life for less than a year in canines and areassociated 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 domainexpression. 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 lastingtherapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cellimmunotherapy in human medicine and its potential applications in animal health, while discussingthe potential of the canine model as a translational system for immuno-oncology research