VSV immunotherapy to improve treatment outcomes in a mouse model of metastatic melanoma

Abstract

Abstract Vesicular Stomatitis Virus (VSV) engineered to express tumor-associated antigens (TAA) is a promising systemic therapy against widely disseminated malignancy. Using a mouse model of metastatic melanoma, we have demonstrated that VSV immunotherapy is a rational addition to current treatment strategies. Combining VSV immunotherapy with adoptive T-cell transfer and localized radiation therapy enhances the overall survival and control of disease in mice challenged with disseminated melanoma. Furthermore, our previous data have shown that the use of stereotactic hypofractionated radiotherapy provides control of subcutaneous localized disease while systemically delivered VSV immunotherapies contribute to the control of metastatic disease. From these experiments we have demonstrated that this therapy is mediated by multiple immune subsets including CD4+, CD8+, and NK1.1+ populations. Thus, we hypothesized that the additional combination of the above clinically relevant therapies with adoptive T-cell transfer and immune checkpoint inhibitors would result in distinct and quantifiable improvements in immunological tumor control. Forthcoming data will characterize the expression dynamics of the inhibitory immune receptors PD-1 and TIM3 on effector and naïve populations (as defined by CD44 and CD62L expression) in response to each of the above therapies in order to design rationale treatment strategies against metastatic melanoma.