Original Project Description:
High-grade B cell lymphoma is a cancer frequently diagnosed in older dogs, with Golden Retrievers and Bernese Mountain Dogs being particularly predisposed. Standard veterinary care involves chemotherapy and while patients initially respond well, the disease proves to be fatal for most dogs diagnosed. In human medicine, chimeric antigen receptor (CAR) T cell therapy, in which the patient’s T lymphocytes are engineered to target and kill their cancer, has been remarkably successful for treating B cell lymphoma. However, a significant number of patients become resistant to this therapy due to loss of target antigen on their cancer cells. To overcome this, next-generation tandem CAR T cells were designed to kill cancer cells by recognizing two separate targets, thereby reducing the ability of cancer cells to escape treatment, and greatly improving the outlook for human patients.
The researchers’ prior work revealed that treatment of canine high-grade B cell lymphoma with CAR T cells is feasible and well tolerated, but they have also seen evidence of cancer cell escape after CAR T therapy in dogs. Thus, the goal of this study is to optimize tandem CAR T cells for dogs diagnosed with high-grade B cell lymphoma and to develop a toolbox for monitoring tandem CAR T cell activity and biosafety for use in future canine CAR T trials. The team envisions that the studies will enable the launch of first-in-canine trials using tandem CAR T cells, thus transforming the currently bleak prognosis for dogs with high-grade canine B cell lymphoma.
Publications:
We remain on track to publish our findings at the end of the funding period.
Presentations:
Although we are still at an early stage of this award, Matt Atherton (PI) has been invited to present at the upcoming Penn Vet Cancer Center External Advisory Board Meeting at the University of Pennsylvania in December 2024. The data generated by the funding provided by CHF will form a significant part of his presentation entitled “A blueprint to develop canine CAR T therapy”. Some of the data generated by the funding provided by CHF has been presented to Penn Vet Cancer Center External Advisory Board Meeting at the University of Pennsylvania in December 2024 by Matt Atherton in a talk entitled “A blueprint to develop canine CAR T therapy”. Brandon Peng also presented
data from this project in the form of a poster at Annual Faculty Research Retreat for University of Pennsylvania, School of Veterinary Medicine in October 2024.
Matt is also excited to share the progress we are making in an invited talk entitled “Fine tuning CAR T therapy for canine hematologic malignancies” to be delivered at AKC Canine Health Foundation National Parent Club Canine Health Conference, CHF 30th Anniversary in Raleigh in August 2025. Matt recently presented some of the data generated in this proposal at an invited seminar at UT Southwestern’s Veterinary Research and Oncology Clinic’s First Annual Symposium entitled “Developing CAR T therapy for canine lymphoma: from the clinic to the lab and back” in June 2025, Matt is also excited to share the progress we are making in an invited talk entitled “Fine tuning CAR T therapy for canine hematologic malignancies” to be delivered at AKC Canine Health Foundation National Parent Club Canine Health Conference, CHF 30th Anniversary in Raleigh in August 2025.
Report to Grant Sponsor from Investigator:
High grade B cell lymphoma is a cancer frequently diagnosed in older dogs, with Golden Retrievers and Bernese Mountain Dogs being particularly predisposed. Standard veterinary care involves chemotherapy and whilst patients initially respond well, the disease proves to be fatal for most dogs diagnosed. In human medicine, chimeric antigen receptor (CAR) T cell therapy, in which the patient’s T lymphocytes are engineered to target and kill their cancer, has been remarkably successful for treating B cell lymphoma. However, a significant number of patients become resistant to this therapy due to loss of target antigen on their cancer cells. To overcome this, next-generation tandem CAR T cells were designed to kill cancer cells by recognizing two separate targets, thereby reducing the ability of cancer cells to escape treatment and greatly improving the outlook for human patients. Our prior work has revealed that treatment of canine high grade B cell lymphoma with CAR T cells is feasible and well tolerated, but we have also seen evidence of cancer cell escape after CAR T therapy in dogs. Thus, the goal of our study is to optimize tandem CAR T cells for dogs diagnosed with high grade B cell lymphoma and to develop a toolbox for monitoring tandem CAR T cell activity and biosafety for use in future canine CAR T trials.
In our fourth progress report we have continued to advance in all aspects of our project. We have confirmed TCAR1 as being the most promising to move forward into trials. Previously we confirmed the presence of the CAR targets in canine patients diagnosed with B cell lymphoma in our clinic. Our recent work has revealed that TCAR1 can effectively kill multiple canine lymphoma cells that reflect subtypes that lose target antigen in the lab, thus reduced likelihood cancer cell escape. Further the development of our toolbox of materials that will allow us to safely assess the activity of our next-generation CAR T cells in future clinical trials is also now complete. Over the next few months, we will perform two more experiments to complete the characterization of TCAR1. Upon completion of these we will document our findings in a technical manuscript and share this with the scientific and wider community.
We are now poised to launch first-in-canine trials using tandem CAR T cells and we are hopeful that with this technology we may be able to transform the way we approach the treatment of canine B cell lymphoma.
CHF 03194 MY2 A Blueprint to Develop Next-Generation CAR T Therapy for Canine Lymphoma