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Theiler's Murine Encephalomyelitis Virus as a Vaccine Candidate for Immunotherapy

By Kevin D. Pavelko, Megan A. Girtman, Yoshihiro Mitsunaga, Yanice V. Mendez-Fernandez, Michael P. Bell, Michael J. Hansen, Kathleen S. Allen, Moses Rodriguez and Larry R. Pease


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

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  1. (2010). 5T4-modified vaccinia Ankara: progress in tumor-associated antigen-based immunotherapy.
  2. (2005). Adenovirus as vehicle for anticancer genetic immunotherapy.
  3. (2003). Amino acid substitutions in VP2 residues contacting sialic acid in low-neurovirulence BeAn virus dramatically reduce viral binding and spread of infection.
  4. (1997). Braininfiltrating cytolytic T lymphocytes specific for Theiler’s virus recognize H2Db molecules complexed with a viral VP2 peptide lacking a consensus anchor residue.
  5. (2010). CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues.
  6. (2008). Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus.
  7. (1991). Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler’s virus.
  8. (2007). Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin.
  9. (2002). Functional activation of myelin-specific T cells by virus-induced molecular mimicry.
  10. (2003). Galactose is needed only for expression of co-receptors used by Theiler’s murine encephalomyelitis virus as the virus does not directly bind galactose or use the UDP-galactose transporter as a receptor.
  11. (2004). Immune responses against adenoviral vectors and their transgene products: a review of strategies for evasion.
  12. (2005). Inability of bm14 mice to respond to Theiler’s murine encephalomyelitis virus is caused by defective antigen presentation, not repertoire selection.
  13. (1989). Infectious cDNA clones of the DA strain of Theiler’s murine encephalomyelitis virus.
  14. (1985). Localization of a neutralization site of Theiler’s murine encephalomyelitis viruses.
  15. (1998). Molecular characterization of a nondemyelinating variant of Daniel’s strain of Theiler’s virus isolated from a persistently infected glioma cell line.
  16. (1999). Molecular evolution of swine vesicular disease virus.
  17. (2002). Mutations that affect the tropism of DA and GDVII strains of Theiler’s virus in vitro influence sialic acid binding and pathogenicity.
  18. (1983). Neonatal infection with the Daniels strain of Theiler’s murine encephalomyelitis virus.
  19. (2007). Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma.
  20. (1983). Persistent infection of oligodendrocytes in Theiler’s virus-induced encephalomyelitis.
  21. (2010). Preparing an oncolytic poliovirus recombinant for clinical application against glioblastoma multiforme.
  22. (1999). Prevalent class I-restricted T-cell response to the Theiler’s virus epitope Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha, gamma interferon, perforin, or costimulation through CD28.
  23. (1999). Prospects and limitations of recombinant poxviruses for prostate cancer immunotherapy.
  24. (2010). Recombination among picornaviruses.
  25. (2008). Replication of Theiler’s virus requires NF-kappa B-activation: higher viral replication and spreading in astrocytes from susceptible mice.
  26. (2009). Saffold virus, a human Theiler’s-like cardiovirus, is ubiquitous and causes infection early in life.
  27. (2001). Serological evidence that Mus musculus is the natural host of Theiler’s murine encephalomyelitis virus.
  28. (1989). Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
  29. (1986). Susceptibility to Theiler’s virusinduced demyelination. Mapping of the gene within the H-2D region.
  30. (2007). The immunodominant CD8+ T cell epitope region of Theiler’s virus in resistant C57BL/6 mice is critical for anti-viral immune responses, viral persistence, and binding to the host cells.
  31. (2000). The leader polypeptide of Theiler’s murine encephalomyelitis virus is required for the assembly of virions in mouse L cells.
  32. (1995). The leader polypeptide of Theiler’s virus is essential for neurovirulence but not for virus growth in BHK cells.
  33. (2001). The leader protein of Theiler’s virus inhibits immediate-early alpha/beta interferon production.
  34. (2004). The leader protein of Theiler’s virus interferes with nucleocytoplasmic trafficking of cellular proteins.
  35. (1992). The role of CD8+T cells in the acute and chronic phases of Theiler’s murine encephalomyelitis virus-induced disease in mice.
  36. (1997). Theiler’s virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes restricted to the same immunodominant VP2 epitope in C57BL/6 mice.
  37. (1998). Theiler’s virus infection of perforin-deficient mice.
  38. (1988). Three spontaneous H-2Db mutants are generated by genetic micro-recombination (gene conversion) events. Impact on the H-2-restricted immune responsiveness.
  39. (2007). Tumor immunoediting and immunosculpting pathways to cancer progression.
  40. (2009). Use of the intracellular fluorescent dye CFSE to monitor lymphocyte migration and proliferation. Curr Protoc Immunol Chapter 4: Unit4 9.
  41. (2003). Variola virus immune evasion proteins.