Research Study Update: Harnessing a Dog's Own Immune System to Kill Lymphoma Tumor Cells

AKC Canine Health Foundation Grant 1418
Principal Investigator: Dr. Heather M. Wilson, DVM; Texas A&M Research Foundation

Study progressing to second round of clinical trials

Lymphoma is the most common malignancy of dogs representing up to 25% of diagnosed cancers. Dogs often develop an aggressive form of lymphoma that is rarely curable, with most unfortunately succumbing to disease within 12 months of diagnosis despite best-available chemotherapies. Dr. Wilson and collaborators sought to develop a new treatment to re-train the dog's own immune system to attack the most common type of canine lymphoma, B-cell lymphoma. In order to accomplish this they obtained a small number of circulating white blood cells, called T cells, from the blood of affected dogs and inserted a gene that will cause the T cell to express a receptor which recognizes the tumor "fingerprint". After docking with the lymphoma, the T cell will be triggered to mount an immune response against the tumor cells with the specific fingerprint. This therapy could be used alone or in combination with chemotherapy.

Dr. Wilson and colleagues at MD Anderson Cancer Center have successfully designed several different canine chimeric antigen receptor (cCARs)-expressing T cells that have mutations that will allow them to target tumor cells. They are currently working with Texas A&M University, the National Institutes of Health and the FDA for approval on the use of these engineered systems to treat pet dogs with B-cell lymphoma.

While they were in the process of optimizing cCAR+ T cell growth and expression, they simultaneously developed CARneg T cells as a successful treatment to significantly extend the survival of chemotherapy-treated dogs with B cell lymphoma (called the P.E.T. 1.0 clinical trial). Regulatory permission was granted for the P.E.T. 1.0 trial by the USDA. They were able to show CARneg T-cell infusion results in rapid killer T-cell reconstitution within a chemotherapy lympho-depleted immune system, CARneg T-cell homing to lymph nodes and tumors, biomarker expression predicting the prognosis of the patient as well as success of the T cell infusion, and a significant increase in tumor-free time and overall survival time. Survival was almost 5 times longer in patients who received T cell infusions after chemotherapy when compared to the chemotherapy only control group. Unfortunately, while survival time was increased with CARneg T-cell infusions post-chemotherapy, the majority of dogs eventually relapsed. Thus, the need to pursue cCAR-expressing T cells to provide long lasting and permanent remission without the need for chemotherapy is still necessary. Studies are ongoing to evaluate the effectiveness of cCAR+ T cells (P.E.T. 2.0 clinical trial).

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