Outbred Canine Model of Adjuvant Immunotherapy for Angiosarcoma
Cutaneous angiosarcoma is a deadly neoplasm of the dermal vascular endothelium that comprises roughly 1% of all soft tissue sarcomas. It is typically locally advanced at presentation, rendering surgical cure difficult and post-surgical metastasis is common. Standard of care includes wide margin excision and intensive wide-field radiotherapy. The use of chemotherapy is controversial though significant palliation can be achieved with doxorubicin and taxane-based regimens. Nonetheless, even the most aggressive standard of care interventions yield abysmal five-year survival rates of only 10-35%. Sarcoma, particularly splenic hemangiosarcoma, is also a devastating and lethal disease among the domestic canine population, accounting for up to 2% of all canine tumors and 1% of all deaths in dogs over the age of ten. Results of previous clinical investigations indicate that immune-based therapies can be a viable option for the treatment of sarcoma in both the adjuvant and therapeutic settings. Given these promising studies, our group intends to file an IND with the FDA for intent to treat cutaneous angiosarcoma using a novel immunotherapeutic approach developed over the last decade and for which we have already filed an IND for intent to treat poor-prognosis brain malignancy in pediatric patients. This immunotherapeutic treatment regimen is based upon novel, patented immunology that enhances the ability of antigen presenting cells to induce a robust Th-1 polarization, generating highly cytotoxic, curative T-cell responses in vivo. The preliminary data indicate that this approach is feasible, safe, and therapeutically efficacious for a variety of different malignancies. Herein, we propose to perform a small-scale veterinary trial of adjuvant immunotherapy for canine splenic hemangiosarcoma so as to test the hypothesis that this regimen is of therapeutic benefit for the treatment of vascular sarcomas. The AIM is to ascertain feasibility, safety, and efficacy of adjuvant immunotherapy in a spontaneous canine model of splenic hemangiosarcoma in conjunction with surgical resection +/- standard of care doxorubicin chemotherapy. By means of this approach, we will generate the meaningful data required for a downstream IND filing as well as characterize the ability of the treatment regimen to provide genuine palliation or cure in canine populations.