title: Theiler's murine encephalomyelitis virus as a vaccine candidate for immunotherapy.
abstract: The induction of sterilizing T-cell responses to tumors is a major goal in the development of T-cell vaccines for treating cancer. Although specific components of anti-viral CD8+ immunity are well characterized, we still lack the ability to mimic viral CD8+ T-cell responses in therapeutic settings for treating cancers. Infection with the picornavirus Theiler's murine encephalomyelitis virus (TMEV) induces a strong sterilizing CD8+ T-cell response. In the absence of sterilizing immunity, the virus causes a persistent infection. We capitalized on the ability of TMEV to induce strong cellular immunity even under conditions of immune deficiency by modifying the virus to evaluate its potential as a T-cell vaccine. The introduction of defined CD8+ T-cell epitopes into the leader sequence of the TMEV genome generates an attenuated vaccine strain that can efficiently drive CD8+ T-cell responses to the targeted antigen. This virus activates T-cells in a manner that is capable of inducing targeted tissue damage and glucose dysregulation in an adoptive T-cell transfer model of diabetes mellitus. As a therapeutic vaccine for the treatment of established melanoma, epitope-modified TMEV can induce strong cytotoxic T-cell responses and promote infiltration of the T-cells into established tumors, ultimately leading to a delay in tumor growth and improved survival of vaccinated animals. We propose that epitope-modified TMEV is an excellent candidate for further development as a human T-cell vaccine for use in immunotherapy.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Pavelko
authors.forename: Megan A
authors.initials: MA
authors.lastname: Girtman
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mitsunaga
authors.forename: Yanice V
authors.initials: YV
authors.lastname: Mendez-Fernandez
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bell
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hansen
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Allen
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D017945:Theilovirus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D017931:DNA Primers; D014765:Viral Vaccines