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Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2001 Dec 01; Vol. 167 (11), pp. 6471-9. - Publication Year :
- 2001
-
Abstract
- Two recombinant Listeria monocytogenes (rLm) strains were produced that secrete the human papilloma virus-16 (HPV-16) E7 protein expressed in HPV-16-associated cervical cancer cells. One, Lm-E7, expresses and secretes E7 protein, whereas a second, Lm-LLO-E7, secretes E7 as a fusion protein joined to a nonhemolytic listeriolysin O (LLO). Lm-LLO-E7, but not Lm-E7, induces the regression of the E7-expressing tumor, TC-1, established in syngeneic C57BL/6 mice. Both recombinant E7-expressing rLm vaccines induce measurable anti-E7 CTL responses that stain positively for H-2D(b) E7 tetramers. Depletion of the CD8+ T cell subset before treatment abrogates the ability of Lm-LLO-E7 to impact on tumor growth. In addition, the rLm strains induce markedly different CD4+ T cell subsets. Depletion of the CD4+ T cell subset considerably reduces the ability of Lm-LLO-E7 to eliminate established TC-1 tumors. Surprisingly, the reverse is the case for Lm-E7, which becomes an effective anti-tumor immunotherapeutic in mice lacking this T cell subset. Ab-mediated depletion of TGF-beta and CD25+ cells improves the effectiveness of Lm-E7 treatment, suggesting that TGF-beta and CD25+ cells are in part responsible for this suppressive response. CD4+ T cells from mice immunized with Lm-E7 are capable of suppressing the ability of Lm-LLO-E7 to induce the regression of TC-1 when transferred to tumor-bearing mice. These studies demonstrate the complexity of L. monocytogenes-mediated tumor immunotherapy targeting the human tumor Ag, HPV-16 E7.
- Subjects :
- Animals
Bacterial Vaccines genetics
CD4-Positive T-Lymphocytes transplantation
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines genetics
Cell Line, Transformed immunology
Cell Line, Transformed pathology
Cell Line, Transformed virology
Cytotoxicity, Immunologic genetics
Epitopes, T-Lymphocyte immunology
Gene Expression Regulation, Viral immunology
Genetic Vectors chemical synthesis
Heat-Shock Proteins genetics
Heat-Shock Proteins immunology
Hemolysin Proteins
Humans
Interferon-gamma physiology
Listeria monocytogenes genetics
Listeria monocytogenes metabolism
Lymphocyte Activation genetics
Mice
Mice, Inbred C57BL
Oncogene Proteins, Viral biosynthesis
Oncogene Proteins, Viral genetics
Oncogene Proteins, Viral metabolism
Papillomaviridae genetics
Papillomavirus E7 Proteins
Spleen cytology
Spleen immunology
Transforming Growth Factor beta immunology
Transforming Growth Factor beta metabolism
Tumor Cells, Cultured immunology
Tumor Cells, Cultured pathology
Tumor Cells, Cultured virology
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Antineoplastic Agents immunology
Bacterial Toxins
Bacterial Vaccines immunology
Cancer Vaccines immunology
Genetic Vectors immunology
Listeria monocytogenes immunology
Oncogene Proteins, Viral immunology
Papillomaviridae immunology
Papillomavirus Vaccines
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 167
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 11714814
- Full Text :
- https://doi.org/10.4049/jimmunol.167.11.6471