Abstract 3291: Development of anti-B7H3 CAR T cells for treatment of osteosarcoma in a canine model

Abstract Characterized as a highly aggressive and metastatic solid bone tumor, osteosarcoma (OS) remains a difficult to treat cancer. Even with the current treatment options of chemotherapy, radiation, and tumor removal surgery there is poor patient prognosis and low survival rates, highlighting the need for novel treatments. Over the last decade, chimeric antigen receptor (CAR) T cells have shown promising results in the treatment of certain leukemias and lymphomas and are further being explored in solid tumor types. We aim to develop CAR T cells against the immune checkpoint cell surface receptor B7H3 (anti-B7H3 CAR T cells), which is over expressed in several cancers, including OS. We hypothesize that anti-B7H3 CAR T cells will be able to successfully lyse osteosarcoma in a canine model. We have verified that B7H3 is expressed and demonstrates significant antibody binding in four canine OS cell lines (D17, CF11, MCKOS, and D22). We have successfully isolated and activated T cells by incubating in CD3 and CD28 coated plates. We will transduce active T cells with anti-B7H3 encoding lentivirus. The cytotoxic effects of anti-B7H3 CAR T cells will be explored in both two-dimensional (2D) and three-dimensional (3D) cell cultures. Additionally, IFNγ, TNFα, and IL-2 cytokine levels will be measured and analyzed. We expect cell lysis and increased cytokine levels post-CAR T therapy in our canine OS cell lines. Citation Format: Theresa Higgins, Payal Agarwal. Development of anti-B7H3 CAR T cells for treatment of osteosarcoma in a canine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3291.