Oncolytic virotherapy for renal cell carcinoma: a novel treatment paradigm?

Introduction: Despite the development of novel targeted therapies, metastatic renal cell carcinoma (mRCC) remains an incurable disease. The known responsiveness of mRCC to immunotherapy and the molecular aberrations characteristic of this disease make it an attractive malignancy for treatment with oncolytic viruses (OVs), as these agents are capable of usurping common oncogenic signaling pathways and generating anti-tumor immune responses. Areas covered: The current evidence to support the use of oncolytic virotherapy against mRCC is discussed with emphasis on the molecular and immunological features of this disease that may be exploited by these biologic agents. Furthermore, the mRCC tumor microenvironment will be detailed to highlight the many OV restrictive factors that exist, which will need to be overcome to realize the full potential of oncolytic virotherapy for this disease. Expert opinion: Preclinical development of OVs for the treatment of mRCC should utilize syngeneic immunocompetent animal models to allow for the assessment of both the anti-viral and anti-tumor immune response generated by these agents in addition to human xenograft models. Furthermore, rationale combination therapies incorporating currently approved mRCC-targeted therapies should be explored as these approaches hold the greatest potential for translating OVs into the clinical arena for use against this disease.