AKCCHF Grant #01418 Abstract


1418: PET 2.0: Providing Engineered T-cells (PET): New Genetic and Immunotherapy Targeting Canines with Spontaneous B-cell Lymphoma (Harnessing a Dog’s Own Immune System to Kill Lymphoma Tumor Cells)

Grant Status: Open
Grant Amount: $150,000.  SCARF contributed $2500.
Dr. Heather M. Wilson, DVM, Texas A&M Research Foundation

Disease(s): Lymphoma

Abstract

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. We seek 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. We plan to obtain a small number of circulating white blood cells, called T cells, from the blood of affected dogs and insert 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. Our preliminary data demonstrate that we can indeed express a desired immunoreceptor in genetically modified T cells and we show that it is possible to harvest and grow T cells in the laboratory and return them safely to the dog. Furthermore, the infused cells can be found in the blood and tumor weeks after infusion, showing that it is possible for these cells to survive in the dog. These data support our plans to develop first-in-dog T-cell therapy targeting a tumor that is basically untreatable.

Publications:

O’Connor CM, Sheppard S, Hartline CA, Huls H, Johnson M, Palla SL, Maiti S, Ma W, Davis RE, Craig S, Lee DA, Champlin R, Wilson H, Cooper LJ. Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy. Sci Rep. 2012;2:24

O’Connor, C. M., & Wilson-Robles, H. (2014). Developing T cell cancer immunotherapy in the dog with lymphoma. ILAR J, 55(1), 169-181.