Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity

Nature Medicine volume 1, pages 1297–1302 (1995)Cite this article

Abstract

Dendritic cells, the most potent ‘professional’ antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In three different well-characterized tumour models, naive mice injected with bone marrow-derived dendritic cells prepulsed with tumour-associated peptides previously characterized as being recognized by class I major histocompatibility complex-restricted cytotoxic T lymphocytes, developed a specific T-lymphocyte response and were protected against a subsequent lethal tumour challenge. Moreover, in the C3 sarcoma and the 3LL lung carcinoma murine models, treatment of animals bearing established macroscopic tumours (up to 1 cm2 in size) with tumour peptide-pulsed dendritic cells resulted in sustained tumour regression and tumour-free status in more than 80% of cases. These results support the clinical use of tumour peptide-pulsed dendritic cells as components in developing effective cancer vaccines and therapies.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Pardoll, D. Tumour antigens: A new look for the 1990s. Nature 369, 357–358 (1994).

    CAS  Article  Google Scholar 

  2. Grabbe, S., Beissert, S., Schwartz, T. & Granstein, R.D. Dendritic ceils as initiators of tumor immune responses: A possible strategy for tumor immunotherapy? Immun. Today 16, 116–120 (1995).

    Google Scholar 

  3. Tamaki, K., Stingl, G., Gullino, M., Sachs, D.H. & Katz, S.I. Ia antigens in mouse skin are predominantly expressed on Langerhans cells. J. Immun. 123, 784–787 (1979).

    CAS  PubMed  Google Scholar 

  4. Razi-Wolf, Z., Falo, L.D. & Reiser, H. Expression and function of the costimulatory molecule B7 on murine Langerhans cells: Evidence for an alternative CTLA-4 ligand. Eur. J. Immun. 24, 805–811 (1994).

    CAS  Article  Google Scholar 

  5. Inaba, K. et al. Identification of proliferating dendritic cell progenitors in mouse blood. J. exp. Med. 175, 1157–1167 (1992).

    CAS  Article  Google Scholar 

  6. Inaba, K. et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. exp. Med. 176, 1693–1702 (1992).

    CAS  Article  Google Scholar 

  7. Caux, C., Dezutter-Dambuyant, C., Schmitt, D. & Banchereau, J. GM-CSF and TNFa cooperate in the generation of dendritic Langerhans cells. Nature 360, 258–261 (1992).

    CAS  Article  Google Scholar 

  8. Caux, C. et al. Potentiation of early hematopoiesis by TNF alpha is followed by inhibition of granulopoietic differentiation and proliferation. Blood 78, 635–644 (1991).

    CAS  PubMed  Google Scholar 

  9. Koch, F. et al. Tumor necrosis factor a maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation. J. exp. Med. 171, 159–171 (1990).

    CAS  Article  Google Scholar 

  10. Romani, N. et al. Proliferating dendritic cell progenitors in human blood. J. exp. Med. 180, 83–93 (1994).

    CAS  Article  Google Scholar 

  11. Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin-4 and downregulated by tumor necrosis factor alpha. J. exp. Med. 179, 1109–1118 (1994).

    CAS  Article  Google Scholar 

  12. Zorina, T. et al. Culture of dendritic cells from murine bone marrow supplemented with GM-CSF and TNF-alpha. J. Immunother. 16, 247 (1994).

    Article  Google Scholar 

  13. Lanier, L.L. et al. CD80(B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J. Immun. 154, 97–105 (1995).

    CAS  PubMed  Google Scholar 

  14. Caux, C. et al. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J. exp. Med. 180, 1841–1847 (1994).

    CAS  Article  Google Scholar 

  15. Mandelboim, O. et al. CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma. Nature 369, 67–71 (1994).

    CAS  Article  Google Scholar 

  16. Feltkamp, M.C.W. et al. Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur. J. Immun. 23, 2242–2249 (1993).

    CAS  Article  Google Scholar 

  17. Falk, K., Rotzschke, O., Stevanovic, S., Jung, G. & Rammensee, H.-G. Allele-specific models revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351, 290–296 (1991).

    CAS  Article  Google Scholar 

  18. Falo, L.D., Kovacsovics-Bankowski, M., Thompson, K. & Rock, K.L. Targeting antigen into the phagocytic pathway In vivo induces protective tumour immunity. Nature Med. 1, 649–653 (1995).

    CAS  Article  Google Scholar 

  19. Porgador, A. & Gilboa, E. Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes. J. exp. Med. 182, 255–260 (1995).

    CAS  Article  Google Scholar 

  20. Gyure, L.A., Barfoot, R., Denham, S. & Hall, J.G. Immunity to a syngeneic sarcoma induced in rats by syngeneic lymph cells exposed to the tumour either in vivo or in vitro. Br. J. Cancer 55, 17–20 (1987).

    CAS  Article  Google Scholar 

  21. Knight, S.C., Hunt, R., Dote, C. & Medawar, P.B. Influence of dendritic cells on tumor growth. Proc. natn. Acad. Sci. U.S.A. 82, 4495–4497 (1985).

    CAS  Article  Google Scholar 

  22. Caux, C., Liu, Y-L. & Banchereau, J. Recent advances in the study of dendritic cells and follicular dendritic cells. Immun. Today 16, 2–4 (1995).

    CAS  Article  Google Scholar 

  23. Grabbe, S. et al. Tumor antigen presentation by murine epidermal cells. J. Immun. 146, 3656–3661 (1991).

    CAS  PubMed  Google Scholar 

  24. Flamand, V. et al. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur. J. Immun. 24, 605–610 (1994).

    CAS  Article  Google Scholar 

  25. Hsu, F.J. et al. Antigen-pulsed dendritic cells are effective in inducing immune responses in patients with B-cell lymphoma. Blood 84, 520a (1994).

    Google Scholar 

  26. Kast, W.M., Boog, C.J.P., Roerp, B.O., Voordouw, A.C. & Melief, C.J.P. Failure or success in the restoration of virus-specific cytotoxic T lymphocyte response defects by dendritic cells. J. Immun. 140, 3186–3193 (1988).

    CAS  PubMed  Google Scholar 

  27. Mizoguchi, H. et al. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258, 1795–1798 (1992).

    CAS  Article  Google Scholar 

  28. Pan, Z.-K., Ikonomidis, G., Lazenby, A., Pardoll, D. & Paterson, Y. A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour cell challenge and causes regression of established tumours. Nature Med. 1, 471–477 (1995).

    CAS  Article  Google Scholar 

  29. Aichele, P., Brduscha-Riem, K., Zinkernagel, R.M., Hengartner, H. & Pircher, H. T cell priming versus T cell tolerance induced by synthetic peptides. J. exp. Med. 182, 261–266 (1995).

    CAS  Article  Google Scholar 

  30. Jenkins, M.K. The ups and downs of T cell costimulation. Immunity 1, 443–446 (1994).

    CAS  Article  Google Scholar 

  31. Bellone, M. et al. In vitro priming of cytotoxic T lymphocytes against poorly immunogenic epitopes by engineered antigen-presenting cells. Eur. J. Immun. 24, 2691–2698 (1994).

    CAS  Article  Google Scholar 

  32. Frassanito, M.A. et al. Identification of Meth A sarcoma-derived class I major histocompatibility complex-associated peptides recognized by a specific CD8+ cytotoxic T lymphocyte. Cancer Res. 55, 124–128 (1995).

    CAS  PubMed  Google Scholar 

  33. Storkus, W.J. & Lotze, M.T. Biology of tumor antigens: Tumor antigens recognized by immune cells. In: Biologic Therapy of Cancer, 2nd edn (eds DeVita, V. T., Hellman, S. & Rosenberg, S.A.) 64–77 (Lippincott, Philadelphia, 1995).

    Google Scholar 

  34. Peoples, G.E. et al. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc. natn. Acad. Sci. U.S.A. 92, 432–436 (1995).

    CAS  Article  Google Scholar 

  35. Bosch, F.X. et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J. natn. Cancer Inst. 87, 796–802 (1995).

    CAS  Article  Google Scholar 

  36. Moore, M.W., Carbone, F.R. & Bevan, M.J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell 54, 777–785 (1988).

    CAS  Article  Google Scholar 

  37. Takahashi, H., Nakagawa, Y., Yokomuro, K. & Berzofsky, J.A. Induction of CD8+ cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells. Int. Immun. 5, 849–857 (1993).

    CAS  Article  Google Scholar 

  38. Rock, K.L., Fleischacker, C. & Gamble, S. Peptide-priming of cytolytic T cell immunity in vivo using (β2-microglobulin as an adjuvant. J. Immun. 150, 1244–1252 (1993).

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Departments of Surgery, Cell Therapeutics, Pathology, Dermatology, and Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA

    J.I. Mayordomo, T. Zorina, W.J. Storkus, L. Zitvogel, C. Celluzzi, L.D. Falo, S.T. Ildstad, A.B. Deleo & M.T. Lotze

  2. Department of Immunohematology and Blood Bank, University Hospital, Leiden, The Netherlands

    C.J. Melief & W. Martin Kast

Authors
  1. J.I. Mayordomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Zorina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W.J. Storkus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Zitvogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Celluzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L.D. Falo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C.J. Melief
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S.T. Ildstad
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W. Martin Kast
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A.B. Deleo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M.T. Lotze
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mayordomo, J., Zorina, T., Storkus, W. et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med 1, 1297–1302 (1995). https://doi.org/10.1038/nm1295-1297

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1295-1297

Further reading

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing