Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus

RM Diaz, F Galivo, T Kottke, P Wongthida, J Qiao… - Cancer research, 2007 - AACR
RM Diaz, F Galivo, T Kottke, P Wongthida, J Qiao, J Thompson, M Valdes, G Barber, RG Vile
Cancer research, 2007AACR
Relatively little attention has been paid to the role of virotherapy in promoting antitumor
immune responses. Here, we show that CD8+ T cells are critical for the efficacy of
intratumoral vesicular stomatitis virus virotherapy and are induced against both virally
encoded and tumor-associated immunodominant epitopes. We tested three separate
immune interventions to increase the frequency/activity of activated antitumoral T cells.
Depletion of Treg had a negative therapeutic effect because it relieved suppression of the …
Abstract
Relatively little attention has been paid to the role of virotherapy in promoting antitumor immune responses. Here, we show that CD8+ T cells are critical for the efficacy of intratumoral vesicular stomatitis virus virotherapy and are induced against both virally encoded and tumor-associated immunodominant epitopes. We tested three separate immune interventions to increase the frequency/activity of activated antitumoral T cells. Depletion of Treg had a negative therapeutic effect because it relieved suppression of the antiviral immune response, leading to early viral clearance. In contrast, increasing the circulating levels of tumor antigen–specific T cells using adoptive T cell transfer therapy, in combination with intratumoral virotherapy, generated significantly improved therapy over either adoptive therapy or virotherapy alone. Moreover, the incorporation of a tumor-associated antigen within the oncolytic vesicular stomatitis virus increased the levels of activation of naïve T cells against the antigen, which translated into increased antitumor therapy. Therefore, our results show that strategies which enhance immune activation against tumor-associated antigens can also be used to enhance the efficacy of virotherapy. [Cancer Res 2007;67(6):2840–7]
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