Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus.
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.
Diaz
Rosa Maria
RM
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Galivo
Feorillo
F
Kottke
Timothy
T
Wongthida
Phonphimon
P
Qiao
Jian
J
Thompson
Jill
J
Valdes
Mikael
M
Barber
Glen
G
Vile
Richard G
RG
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D050130:Oncolytic Virotherapy / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*