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Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine and human patients, but the actual action mechanism has never been described in patients. It is of importance to determine whether MSCs infected with OAds can reach the tumor and release the virus in a clinical setting. For this purpose, GFP-labeled MSCs were infected with an OAd and inoculated into a companion dog diagnosed with spontaneous lung carcinoma. Forty-eight hours later, the tumor was excised and analyzed microscopically by flow cytometry for GFP fluorescence detection, and a cellular culture was established. Peripheral blood samples were taken to quantify the oncolytic adenovirus by qRT-PCR. Green fluorescence cells detected in the cellular culture by microscopy and flow cytometry revealed 0.69% GFP-positive cells in the tumor. OAd in peripheral blood was confirmed by qRT-PCR during follow-up. For the first time, the tumoral-homing capacity of OAds infected-MSC has been confirmed in a clinical setting, helping to explain the clinical response mechanism, whose efficacy was previously reported in canine and human patients.

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.