Radiation Therapy Combined with Cowpea Mosaic Virus Nanoparticle in Situ Vaccination Initiates Immune-Mediated Tumor Regression.

Abstract

Epithelial ovarian cancer is a deadly gynecologic malignancy because of its late detection, usually after local and distant metastatic spread. These cancers develop resistance to traditional chemotherapeutic agents; therefore, the development of next-generation immunotherapeutic approaches may have a significant promise in improving outcomes. A novel immunotherapeutic approach utilizing combination radiation therapy (RT) with immunostimulatory cowpea mosaic virus (CPMV) was tested in a preclinical syngeneic mouse model of ovarian carcinoma. ID8-Defb29/Vegf tumors were generated in C57BL/6 mice. Compared to placebo-treated control tumors or those treated with a single agent RT or CPMV, the combination treatment resulted in a significantly improved tumor growth delay (p < 0.05). Additionally, immunohistochemical profiling of tumor samples after treatment with CPMV demonstrated an increase in tumor infiltrating lymphocytes (TILs). These results suggest that utilizing CPMV particles in combination with RT can turn an immunologically “cold” tumor (with low number of TILs) into an immunologically “hot” tumor. This novel combination treatment approach of RT and CPMV demonstrated the ability to control tumor growth in a preclinical ID8 ovarian cancer model, showing promise as an in situ tumor vaccine and warrants further testing.