Theresa
Higgins

Development of anti-B7H3 CAR T cells for treatment of osteosarcoma in a canine model

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Authors:

Theresa Higgins

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Osteosarcoma (OS) is a highly metastatic and difficult-to-treat bone cancer that, in humans, predominantly affects children and adolescents, but also spontaneously occurs in dogs. Despite the current treatments of chemotherapy and radiation, prognosis is still poor, and there are low patient five-year survival rates in humans and even lower one-year survival rates in dogs. Therefore, novel treatments are critical to explore to improve treatment options. Chimeric Antigen Receptor (CAR) T cells are re-programmed to target cancer-specific receptors and have shown immense promise in the treatment of lymphomas and leukemias. However, their effects in solid tumors are still being explored. We are developing CAR T cells against the surface receptor B7H3 (anti-B7H3 CAR T cells), which is upregulated in malignant tumors, such as osteosarcoma, which we hypothesize will be able to lyse osteosarcoma cells in a canine model. We have successfully isolated and activated canine T cells using anti-CD3 and anti-CD28 antibodies and will transduce these activated cells with anti-B7H3 scfv encoding retrovirus. The cytotoxic effects will be observed in both 2D and 3D cell cultures in four separate GFP- luciferase-expressing canine osteosarcoma cell lines (D17, CF11, MCKOS, and D22) using fluorescent microscopy and luminescence assays. We expect this study to provide insight into improving canine osteosarcoma treatment as well as the potential for translational impacts in human medicine.

Source:

Auburn University / College of Veterinary Medicine / 2025

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Theresa Higgins