Listeria-Based Vaccine Targeting Interferon-Stimulated Gene 15 for Renal Cell Carcinoma

Interferon-stimulated gene 15 (ISG15) is the first identified ubiquitin-like modifier and has been implicated in its central role in innate immunity against intracellular pathogens. Interestingly, there is a growing body of evidence that demonstrated the role of ISG15 in cancer progression. Here, we investigate the role of ISG15 in renal cell carcinomas (RCC). We found that ISG15 is highly expressed RCC tumors compared to normal kidneys and is significantly associated with an unfavorable prognosis. In subcutaneous syngeneic RCC mouse models, vaccination of Lm-LLO-ISG15 intraperitoneally significantly reduces tumor growth rate and final tumor mass. Lm-LLO-ISG15 inflames and modulates the immunologic profiles of the tumor microenvironment (TME) by increasing the number of tumor-infiltrating functional T cells. Our initial findings suggest that ISG15 is a novel cancer-associated antigen in RCC and can be targeted by means of Listeria-based vaccines.