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 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.
Kim
Tae-Yoon
TY
Department of Dermatology, The Catholic University of Korea, Seoul 137-040, Korea.
Myoung
Han-Jeong
HJ
Kim
Ji-Hyun
JH
Moon
In-Sung
IS
Kim
Tai-Gyu
TG
Ahn
Woong-Shick
WS
Sin
Jeong-Im
JI
D000818:Animals; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002461:Cell Line, Transformed; D018899:CpG Islands / Q000276:immunology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000276:immunology* / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D012097:Repressor Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology
D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D007074:Immunoglobulin G; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma