Intratumoral STING agonist therapy as a potential bridge to surgery in canine sarcoma

Background Sarcomas are rare and aggressive malignancies in humans. Management of sarcoma primarily involves surgical intervention with neoadjuvant radiotherapy. Many sarcomas are refractory to existing immunotherapies. Recent studies in murine sarcoma have shown that activation of the stimulator of interferon genes pathway (STING) can induce tumor eradication. Although sarcomas are rare in humans, they occur frequently in dogs. Studying STING therapy in canine sarcoma patients provides a unique opportunity to explore a clinically translational animal model that recapitulates tumor size and clinical progression of human disease. Methods Four sarcoma-bearing dogs were recruited for this study. All subjects underwent weekly intratumoral STING therapy until a surgical or humane-endpoints were reached. Tumor volume, vital signs, and weight were measured at each visit. Two STING agonists were studied (ADU-S100 – CDN and E7766). Sera were collected prior to and 6h following STING immunotherapy to measure systemic cytokine levels. Histologic assessment of tumors was completed at time of biopsy or necropsy. Results All dogs experienced a reduction in tumor volume. Two dogs became surgical candidates following STING treatment. Overall survival varied between 14–736 days among treated dogs. Systemic cytokine elevation was observed following STING therapy. At time of necropsy, none of the dogs showed macroscopic evidence of metastatic disease. Conclusions Intralesional STING immunotherapy is a feasible treatment for dogs with sarcoma, demonstrating biological activity enabling surgical intervention in 2/4 dogs. At time of necropsy, no metastatic disease was observed. Future prospective cohort studies should be completed to further investigate this translational immunotherapy.