Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells : Involvement of CD4+ and CD8+ T cells in protection

An important goal of immunotherapy against human papillomavirus (HPV) infection and the cervical cancer is to control viral infection and the cancer cell growth. Here we investigate the utility of HPV 16 E7 along with CpG-oligodeoxynucleotide (ODN) for protection against HPV-immortalized tumor cells...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-12, Vol.62 (24), p.7234-7240
Main Authors: KIM, Tae-Yoon, MYOUNG, Han-Jeong, KIM, Ji-Hyun, MOON, In-Sung, KIM, Tai-Gyu, AHN, Woong-Shick, SIN, Jeong-Im
Format: Article
Language:English
Subjects:
Animals
Antibody Specificity
Antineoplastic agents
Biological and medical sciences
Cancer Vaccines - immunology
Cancer Vaccines - pharmacology
Carcinogenesis, carcinogens and anticarcinogens
Cell Line, Transformed
Chemical agents
Chemotherapy
CpG Islands - immunology
Female
Immunization
Immunoglobulin G - biosynthesis
Immunoglobulin G - classification
Immunoglobulin G - immunology
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Lung Neoplasms - immunology
Lung Neoplasms - prevention & control
Lung Neoplasms - virology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Medical sciences
Mice
Mice, Inbred C57BL
Oligonucleotides - immunology
Oligonucleotides - pharmacology
Oncogene Proteins, Viral - biosynthesis
Oncogene Proteins, Viral - genetics
Oncogene Proteins, Viral - immunology
Oncogene Proteins, Viral - pharmacology
Papillomaviridae - immunology
Papillomavirus E7 Proteins
Papillomavirus Infections - immunology
Pharmacology. Drug treatments
Recombinant Proteins - biosynthesis
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Recombinant Proteins - pharmacology
Repressor Proteins
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Cytotoxic - drug effects
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
Th1 Cells - drug effects
Th1 Cells - immunology
Th1 Cells - metabolism
Tumor Cells, Cultured
Tumor Virus Infections - immunology
Tumors
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Summary:An important goal of immunotherapy against human papillomavirus (HPV) infection and the cervical cancer is to control viral infection and the cancer cell growth. Here we investigate the utility of HPV 16 E7 along with CpG-oligodeoxynucleotide (ODN) for protection against HPV-immortalized tumor cells using an animal model. E7+ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels. However, no such effect was observed without addition of both E7 and ODN. We additionally evaluated levels of immune responses by E7+ODN coinjection. E7+ODN resulted in E7-specific antibody (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell proliferative responses significantly higher than E7 alone. However, CTL responses were induced only by E7+ODN. Moreover, IFN-gamma production was detected only in E7+ODN immunized groups in which IFN-gamma releasing CD4+ (T-helper 1 type) and CD8+ T cells (CTL) were induced only by E7+ODN. Moreover, tumor protection appears to be mediated by CD4+ and in most CD8+ T cells, as determined by in vivo T-cell subset depletion. Taken together, these data suggest that E7+ODN codelivery could be an effective approach to induce E7-specific protective immune responses as a possible immunotherapeutic strategy for cervical cancer.
ISSN:0008-5472
1538-7445