Theiler's Murine Encephalomyelitis Virus as a Vaccine Candidate for Immunotherapy
| Autor: | Megan A. Girtman, Larry R. Pease, Moses Rodriguez, Yanice V. Mendez-Fernandez, Michael J. Hansen, Kathleen S. Allen, Yoshihiro Mitsunaga, Kevin D. Pavelko, Michael P. Bell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cellular immunity
medicine.medical_treatment viruses lcsh:Medicine Polymerase Chain Reaction Mice 0302 clinical medicine lcsh:Science Immune Response 0303 health sciences Multidisciplinary Attenuated vaccine Viral Vaccine Immunizations 3. Good health 030220 oncology & carcinogenesis Theilovirus Immunotherapy Research Article Tumor Immunology Immunology Molecular Sequence Data Biology Microbiology Virus Immunomodulation 03 medical and health sciences Immune system Immunity Virology medicine Animals Amino Acid Sequence Immunity to Infections 030304 developmental biology DNA Primers Base Sequence Sequence Homology Amino Acid lcsh:R Immune Defense Viral Vaccines Immunologic Subspecialties Mice Inbred C57BL lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 5, p e20217 (2011) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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