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One obstacle for human solid tumor immunotherapy research is the lack of clinically relevant animal models. In this study, we sought to establish a CAR T cell treatment model for naturally occurring canine sarcomas as a model for human CAR T cell therapy. Canine CARs specific for B7-H3 were constructed using a single chain variable fragment derived from the human B7-H3-specific antibody MGA271, which we confirmed to be cross-reactive with canine B7-H3. After refining activation, transduction and expansion methods, we confirmed target killing in a tumor spheroid 3D assay. We designed a B7-H3 canine CAR T cell and achieved consistently high levels of transduction efficacy, expansion and in vitro tumor killing. Safety of the CAR T cells were confirmed in two purposely bred healthy canine subjects following lymphodepletion by cyclophosphamide and fludarabine. Immune response, clinical parameters and manifestation were closely monitored post treatments and were shown to resemble that of humans. No severe adverse events were observed. In summary, we demonstrated that similar to human cancers, B7-H3 can serve as a target for canine solid tumors. We successfully generated highly functional canine B7-H3-specific CAR T cell products using a production protocol that closely models human CAR T cell production procedure. The treatment regimen that we designed was confirmed to be safety in vivo. Our research provides a promising direction to establish in vitro and in vivo models for immunotherapy for canine and human solid tumor treatment.

B7-H3 Specific CAR T Cells for the Naturally Occurring, Spontaneous Canine Sarcoma Model