Safety and Efficacy of an Oncolytic Adenovirus as an Immunotherapy for Canine Cancer Patients

SIMPLE SUMMARY: The use of oncolytic virus is an innovative approach that has shown promising results as a treatment in oncology. Epithelial-derived tumors are the most frequent neoplasms in dogs, but gold standard therapies can be highly invasive procedures. Due to the accessible localization of these tumors, the intratumoral administration is feasible. Therefore, we propose to determine the safety and efficacy of intratumoral administration of oncolytic adenovirus ICOCAV15, in canine patients with epithelial-derived tumors. Eight dogs with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15. No clinically relevant changes were observed in the blood count, biochemistry and coagulation test analyzed during follow-up. The survival time of the 6/8 dogs exceeded the median survival time with chemotherapy, showing a partial response rate of 25% and 75% of stable disease. ICOCAV15 was detected in the target lesion by qPCR and immunohistochemistry. Also, some of the non-treated metastasis showed an infiltration of ICOCAV15 by immunohistochemistry. The immune populations were evaluated, and an increase of CD8+, MAC387+, CD3+ and CD20+ cells was reported in some of the patients after the inoculation. These results show that intratumoral ICOCAV15 is safe and well tolerated by dogs. Also, they suggest ICOCAV15 could be a new tool in veterinary oncology for accessible carcinomas/adenocarcinomas. ABSTRACT: The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment’s safety, a blood count, biochemistry, and coagulation test were performed before treatment and during follow-up. Immune populations were analyzed by flow cytometry. Anti-adenovirus antibodies were also determined. The immune infiltration, vascularization, and viral presence in the tumor were determined by CD3, CD4, CD20, CD31 and CAV by immunohistochemistry. All the dogs maintained a good quality of life during follow-up, and some had increased median survival time when compared with dogs treated with chemotherapy. No treatment-related adverse effects were detected. The Response Evaluation Criteria In Solid Tumors criteria were also assessed: two patients showed a partial response and the rest showed stable disease at various times during the study. ICOCAV15 was detected inside the tumor during follow-up, and antiviral antibodies were detected in all patients. Furthermore, the tumor-infiltrating immune cells increased after viral administration. Therefore, we suggest that intratumorally administered ICOCAV15 could represent as a new tool for the treatment of canine carcinoma because it is safe, well-tolerated by dogs, and shows promising results.