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

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.

Newcastle disease virus LaSota strain induces apoptosis and activates the TNFα/NF‐κB pathway in canine mammary carcinoma cells

“…26,46,47 Dogs are not the natural hosts of NDV and have no vaccinationassociated immunity compared to OVs such as canine distemper virus (CDV) and canine adenovirus (CAV). 48,49 In addition, NDV replicates selectively and efficiently in tumour cells, and replicates in the cytoplasm without integrating with the cell genome. 15 These characteristics support the safety of NDV making it a promising oncolytic agent.…”

Improved characterization and translation of NK cells for canine immunotherapy

“…Martín-Carrasco et al tested an intratumor oncolytic virus based on canine wild-type adenovirus which was engineered to selectively replicate in mutated cells to treat canine patients with cancer ( 24 ). The strength of the study was the availability of serial sample collections from patients before and up to one year after treatment.…”

“…The strength of the study was the availability of serial sample collections from patients before and up to one year after treatment. At least four of the eight patients had an increase in peripheral NK cells within the first month after treatment as assessed by flow cytometry ( 24 ). However, CD56 was used as the identifying marker, which is not known to be expressed on canine NK cells, highlighting the importance of validating both the reagents used as well as the underlying biology given the extensive cross-species differences in NK cells.…”

Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors

“… 7 , 8 , 9 , 10 , 11 , 12 Dogs with spontaneous cancers appear to be valuable models to evaluate the efficacy of OVs. 13 , 14 , 15 , 16 , 17 Therefore, safety and efficacy evaluation of OVs in canine cancers should be considered to assess their potential benefit in human medicine. Safety, biodistribution, and shedding of TG6002 has been established in healthy dogs.…”