Skip to main content

Advertisement

Log in

Vaccination With OK-432 Followed by TC-1 Tumor Lysate Leads to Significant Antitumor Effects

  • Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4+ T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4+ T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–19.

    Article  CAS  PubMed  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  3. Itoh T, Ueda Y, Okugawa K, et al. Streptococcal preparation OK432 promotes functional maturation of human monocyte-derived dendritic cells. Cancer Immunol Immunother. 2003;52(4):207–214.

    Article  CAS  PubMed  Google Scholar 

  4. Ono T, Kurata S, Wakabayashi K, Sugawara Y, Saito M. Inhibitory effect of a streptococcal preparation (OK-432) on the nucleic acid synthesis in tumor cells in vitro. Gann Gan. 1973;64(1):59–64.

    CAS  PubMed  Google Scholar 

  5. Oshimi K, Kano S, Takaku F, Okumura K. Augmentation of mouse natural killer cell activity by a streptococcal preparation, OK-432. J Nation Cancer Ins. 1980;65(6):1265–1269.

    CAS  Google Scholar 

  6. Saito M, Nanjo M, Kataoka M, et al. Adoptive immunotherapy by pantropic killer cells recovered from OK-432-injected tumor sites in mice. Cancer Res. 1988;48(15):4163–4167.

    CAS  PubMed  Google Scholar 

  7. Saito M, Nanjo M, Aonuma E, et al. Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432. Int J Cancer. 1984;33(2):271–276.

    Article  CAS  PubMed  Google Scholar 

  8. Shitara K, Ichimura O, Mitsuno T, Osawa T. Natural killer (NK) cell activating factor released from murine thymocytes stimulated with an anti-tumor streptococcal preparation, OK-432. J Immunol. 1985;134(2):1039–1047.

    CAS  PubMed  Google Scholar 

  9. Wakasugi H, Kasahara T, Minato N, Hamuro J, Miyata M, Morioka Y. In vitro potentiation of human natural killer cell activity by a streptococcal preparation, OK-432: interferon and interleukin-2 participation in the stimulation with OK-432. J Nation Cancer Ins. 1982;69(4):807–812.

    CAS  Google Scholar 

  10. Kitsuki H, Katano M, Ikubo A, et al. Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-gamma in enhancement of surface expression of ICAM-1 on tumor cells in vivo. Clinical Immunol Immunopathol. 1996;78(3):283–290.

    Article  CAS  Google Scholar 

  11. Okamoto T, Harada M, Tamada K, et al. Local injection of OK432 can augment the TH1-type T-cell response in tumor-draining lymph node cells and increase their immunotherapeutical potential. Int J Cancer. 1997;70(5):598–605.

    Article  CAS  PubMed  Google Scholar 

  12. Ryoma Y, Moriya Y, Okamoto M, Kanaya I, Saito M, Sato M. Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy. Anticancer Res. 2004;24(5C):3295–3301.

    CAS  PubMed  Google Scholar 

  13. Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer Immunol Immunother. 2008;57(10):1511–1521.

    Article  CAS  PubMed  Google Scholar 

  14. Lin CT, Tsai YC, He L, et al. DNA vaccines encoding IL-2 linked to HPV-16 E7 antigen generate enhanced E7-specific CTL responses and antitumor activity. Immunol Lett. 2007;114(2):86–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nature Rev. 2002;2(5):342–350.

    Google Scholar 

  16. Lin CT, Hung CF, Juang J, et al. Boosting with recombinant vaccinia increases HPV-16 E7-Specific T cell precursor frequencies and antitumor effects of HPV-16 E7-expressing Sindbis virus replicon particles. Mol Ther. 2003;8(4):559–566.

    Article  CAS  PubMed  Google Scholar 

  17. Wu A, Zeng Q, Kang TH, et al. Innovative DNA vaccine for human papillomavirus (HPV)-associated head and neck cancer. Gene Ther. October 2010. Epub ahead of print.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Lin CT, Yen TC, Chang TC, et al. Role of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in re-recurrent cervical cancer. Int J Gynecol Cancer. 2006;16(6):1994–2003.

    Article  PubMed  Google Scholar 

  19. Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med. 1998;4(3):321–327.

    Article  CAS  PubMed  Google Scholar 

  20. Hohn H, Pilch H, Gunzel S, et al. CD4+ tumor-infiltrating lymphocytes in cervical cancer recognize HLA-DR-restricted peptides provided by human papillomavirus-E7. J Immunol. 1999;163(10):5715–5722.

    CAS  PubMed  Google Scholar 

  21. Heard I, Schmitz V, Costagliola D, Orth G, Kazatchkine MD. Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy. AIDS (London, England). 1998;12(12):1459–1464.

    Article  CAS  Google Scholar 

  22. Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature. 2003;421(6925):852–856.

    Article  CAS  PubMed  Google Scholar 

  23. Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science (New York, NY). 2003;300(5617):337–339.

    Article  CAS  Google Scholar 

  24. Sun JC, Bevan MJ. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science (New York, NY). 2003;300(5617):339–342.

    Article  CAS  Google Scholar 

  25. van de Berg PJ, van Leeuwen EM, ten Berge IJ, van Lier R. Cytotoxic human CD4(+) T cells. Curr Opin Immunol. 2008;20(3):339–343.

    Article  PubMed  CAS  Google Scholar 

  26. Okamoto M, Oh EG, Oshikawa T, et al. Toll-like receptor 4 mediates the antitumor host response induced by a 55-kilodalton protein isolated from Aeginetia indica L., a parasitic plant. Clin Diagnos lab Immunol. 2004;11(3):483–495.

    CAS  Google Scholar 

  27. Koido S, Hara E, Homma S, et al. Streptococcal preparation OK-432 promotes fusion efficiency and enhances induction of antigen-specific CTL by fusions of dendritic cells and colorectal cancer cells. J Immunol. 2007;178(1):613–622.

    Article  CAS  PubMed  Google Scholar 

  28. Mashino K, Sadanaga N, Tanaka F, Ohta M, Yamaguchi H, Mori M. Effective strategy of dendritic cell-based immunotherapy for advanced tumor-bearing hosts: the critical role of Th1-dominant immunity. Mol Cancer Therap. 2002;1(10):785–794.

    CAS  Google Scholar 

  29. Schultz ES, Chapiro J, Lurquin C, et al. The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. J Exp Med. 2002;195(4):391–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Robinson DS, O’Garra A. Further checkpoints in Th1 development. Immunity. 2002;16(6):755–758.

    Article  CAS  PubMed  Google Scholar 

  31. Kurosawa S, Harada M, Shinomiya Y, Terao H, Nomoto K. The concurrent administration of OK432 augments the antitumor vaccination effect with tumor cells by sustaining locally infiltrating natural killer cells. Cancer Immunol Immunother. 1996;43(1):31–38.

    Article  CAS  PubMed  Google Scholar 

  32. Zamai L, Ponti C, Mirandola P, Gobbi G, Papa S, Galeotti L, et al. NK cells and cancer. J Immunol. 2007;178(7):4011–4016.

    Article  CAS  PubMed  Google Scholar 

  33. Kobayashi M, Fitz L, Ryan M, et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989;170(3):827–845.

    Article  CAS  PubMed  Google Scholar 

  34. Okamoto M, Kaji R, Kasetani H, et al. Purification and characterization of interferon-gamma-inducing molecule of OK-432, a penicillin-killed streptococcal preparation, by monoclonal antibody neutralizing interferon-gamma-inducing activity of OK-432. J Immunother Emphasis Tumor Immunol. 1993;13(4):232–242.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheng-Tao Lin MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, IJ., Yen, CF., Lin, KJ. et al. Vaccination With OK-432 Followed by TC-1 Tumor Lysate Leads to Significant Antitumor Effects. Reprod. Sci. 18, 687–694 (2011). https://doi.org/10.1177/1933719110396230

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719110396230

Navigation