Pilot Study of Intratumoral Immunotherapy with Cowpea Mosaic Virus Nanoparticles: Safety in Refractory Canine Oral Tumors

Abstract

Oral tumors (squamous cell carcinoma, malignant melano ma, and fibrosarcoma) represent 6¿7% of all canine cancers. Given that these tumors have a high local recurrence rate and metastatic potential, conventional therapies have suboptimal response rates, leading to poor patient outcomes. Here, we report the use of intratumoral virus-like particles from cowpea mosaic virus (CPMV) in four canine patients with recurrent oral malignant tumors and lymph node metastasis. All tumors were nonresponders to chemotherapy and had a mild initial response to CPMV intratumoral immunotherapy without any serious immune-related adverse effects. None of the patients developed pulmonary metastasis during follow-up, although local progression was seen in all the patients. Furthermore, tumor-infiltrated immune T cells increased in number after the intratumoral immunotherapy with CPMV, suggesting activation of the tumor microenvironment. All the patients had a rapid decrease in the tumor-promoting chemokines IL-8 and CXCL1, which could indicate that a decrease in metastatic potential could have been generated by the CPMV immunotherapy. The increased number of infiltrated immune cells, the decrease in some pro-tumoral chemokines, and the absence of adverse effects suggest that CPMV could be a safe treatment and should be further explored as a novel therapy for canine oral tumors.