Abstract
Vaccinia vaccines have become important vectors for antigen-specific immunotherapy. Calreticulin has been shown to enhance MHC class I presentation of linked peptide/protein and may be useful for antigen-specific cancer treatment. An innovative vaccine administering antigen linked to calreticulin via a vaccinia vector may generate a potent antigen-specific antitumor response. We tested the efficacy of linking calreticulin (CRT) to model antigen human papilloma virus type 16 (HPV-16) E7 in the context of a vaccinia vaccine (Vac-CRT/E7). Intraperitoneal vaccination of C57BL/6 mice with Vac-CRT/E7 led to a dramatic increase in E7-specific IFN-gamma-secreting CD8+ T cells and a potent antitumor effect against E7-expressing tumors compared to immunization with Vac-E7 or Vac-CRT. When compared to other chimeric vaccinia vaccines employing various intracellular targeting strategies previously developed in our lab, Vac-CRT/E7 elicited the highest number of E7-specific CD8+ T cells. Thus, vaccination with vaccinia expressing CRT linked to a tumor antigen may represent an advantageous strategy for cancer immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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Calreticulin / genetics
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Calreticulin / immunology*
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Cancer Vaccines* / genetics
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Cancer Vaccines* / immunology
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Cancer Vaccines* / therapeutic use
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Cell Line, Transformed
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Genetic Vectors
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Interferon-gamma / analysis
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Mice
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Mice, Inbred C57BL
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Neoplasm Transplantation
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Neoplasms, Experimental / immunology
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Neoplasms, Experimental / therapy*
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology*
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Papillomaviridae
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Papillomavirus E7 Proteins
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Vaccination
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Vaccines, DNA / immunology
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Vaccines, DNA / therapeutic use
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Vaccines, Synthetic / therapeutic use
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Vaccinia virus / genetics
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Vaccinia virus / immunology*
Substances
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Calreticulin
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Cancer Vaccines
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Recombinant Proteins
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Vaccines, DNA
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Vaccines, Synthetic
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oncogene protein E7, Human papillomavirus type 16
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Interferon-gamma