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Applications and Opportunities for Immune Cell CAR Engineering in Comparative Oncology
Antonia Rotolo1, Matthew J Atherton2
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania.
Summary
Canine cancer models offer a unique platform for advancing chimeric antigen receptor (CAR) T-cell therapy for solid tumors. Studying CAR T-cell treatments in pet dogs provides crucial data to improve human clinical trials.
Area of Science:
- Immunology
- Oncology
- Comparative Medicine
Background:
- Chimeric antigen receptor (CAR) T-cell therapy has revolutionized human hematologic cancer treatment but faces challenges in solid tumors.
- Spontaneously occurring cancers in pet dogs share biological and clinical similarities with human malignancies, making them valuable models.
- Dogs' immunocompetency, genetic diversity, and shared environment with humans enhance their utility for preclinical CAR T-cell therapy research.
Purpose of the Study:
- To explore the potential of pet dogs as a model for optimizing CAR T-cell therapy, particularly for solid tumors.
- To identify and address challenges in canine CAR T-cell trials that mirror human trial issues.
- To highlight emerging adoptive cell therapy strategies in dogs and their role in supporting human clinical trials.
Main Methods:
- Reviewing challenges encountered in early canine lymphoma CAR T-cell trials, including manufacturing, persistence, and antigen escape.
- Examining ongoing adoptive cell therapy investigations in dogs with hematological and solid cancers.
- Analyzing data from canine studies to identify predictive biomarkers for CAR T-cell therapy response.
Main Results:
- Early canine CAR T-cell trials for lymphoma exhibited challenges similar to those in human trials.
- Emerging canine studies are evaluating novel CAR T-cell regimens for both blood cancers and solid tumors.
- Canine models are demonstrating potential for identifying effective CAR T-cell strategies and biomarkers.
Conclusions:
- Canine models with spontaneous cancers serve as effective platforms for testing innovative CAR T-cell approaches.
- Data from canine immunotherapy studies can significantly inform and improve the design of human clinical trials.
- Advancing canine immunotherapy research through increased funding and multi-institutional collaboration will benefit both human and canine cancer patients.
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