03194: A Blueprint to Develop Next-Generation CAR T Therapy for Canine Lymphoma
Grant Status: Open
One Health: Yes
Abstract
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.
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