title: Systemic combination virotherapy for melanoma with tumor antigen-expressing vesicular stomatitis virus and adoptive T-cell transfer.
abstract: Oncolytic virotherapy offers the potential to treat tumors both as a single agent and in combination with traditional modalities such as chemotherapy and radiotherapy. Here we describe an effective, fully systemic treatment regimen, which combines virotherapy, acting essentially as an adjuvant immunotherapy, with adoptive cell transfer (ACT). The combination of ACT with systemic administration of a vesicular stomatitis virus (VSV) engineered to express the endogenous melanocyte antigen glycoprotein 100 (gp100) resulted in regression of established melanomas and generation of antitumor immunity. Tumor response was associated with in vivo T-cell persistence and activation as well as treatment-related vitiligo. However, in a proportion of treated mice, initial tumor regressions were followed by recurrences. Therapy was further enhanced by targeting an additional tumor antigen with the VSV-antigen + ACT combination strategy, leading to sustained response in 100% of mice. Together, our findings suggest that systemic virotherapy combined with antigen-expressing VSV could be used to support and enhance clinical immunotherapy protocols with adoptive T-cell transfer, which are already used in the clinic.
authors: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Diana M
authors: DM
authors: Rommelfanger
authors: Phonphimon
authors: P
authors: Wongthida
authors: Rosa M
authors: RM
authors: Diaz
authors: Karen M
authors: KM
authors: Kaluza
authors: Jill M
authors: JM
authors: Thompson
authors: Timothy J
authors: TJ
authors: Kottke
authors: Richard G
authors: RG
authors: Vile
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D050130:Oncolytic Virotherapy / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D058951:gp100 Melanoma Antigen / Q000276:immunology*
chemical_list: D058951:gp100 Melanoma Antigen