Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides (original) (raw)

Nature Medicine volume 1, pages 1179–1183 (1995)Cite this article

Abstract

The cure of micrometastases following surgery is the major goal of cancer immunotherapy. We have recently isolated tumour-associated antigen (TAA) peptides, MUT 1 and MUT 2, derived from a mutated connexin 37 gap-junction protein, from the malignant 3LL-D122 murine lung carcinoma. We now report that synthetic MUT 1 or MUT 2 induces effective antitumour cytoxic T lymphocytes. Peptide vaccines protect mice from spontaneous metastases of 3LL-D122 tumours. Moreover, peptide vaccines reduce metastatic loads in mice carrying pre-established micrometastases. Tumour-specific immunity was primarily mediated by CD8+ T cells. This is the first evidence that peptide therapy may be effective in treatment of residual tumours and provides a rationale for the development of peptide vaccines as a modality for cancer therapy.

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References

  1. Urban, J.L. & Schreiber, H. Tumor antigens. Annu. Rev. Immun. 10, 617–644 (1992).
    Article CAS Google Scholar
  2. Dranoff, G. et al. Vaccination with irradiated tumor _Cell_s engineered to secrete murine granulocyte macrophage colony-stimulating factor stimulates potent, specific and long lasting anti-tumor immunity. Proc. natn. Acad. Sci. U.S.A. 90, 3539–3543 (1993).
    Article CAS Google Scholar
  3. Melief, C.J. Tumor eradication by adoptive transfer of cytotoxic T lymphocytes. Adv. Cancer Res. 58, 143–175 (1992).
    Article CAS Google Scholar
  4. Rosenberg, S.A. et al. Use of tumor infiltrating lymphocytes and interlukin-2 in the immunotherapy of patients with metastatic melanoma. New Engl. J. Med. 319, 1676–1680 (1988).
    Article CAS Google Scholar
  5. Boon, T., Cerottini, J.C., Van Der Eynde, B., Van Der Brugenn, P. & Van Pel, A. Tumor antigens recognized by T lymphocytes. Annu Rev. Immun. 12, 337–365 (1994).
    Article CAS Google Scholar
  6. Mandelboim, O. et al. CTL induction by a tumor associated antigen octapeptide derived from a murine lung carcinoma Nature 369, 67–71 (1994).
    Article CAS Google Scholar
  7. Plaksin, D., Gelber, C., Feldman, M. & Eisenbach, L. Reversal of the metastatic phenotype in Lewis lung carcinoma cells following transfection with syngeneic H–2Kb gene. Proc. natn. Acad Sci. U.S.A. 85, 4463–4467 (1988).
    Article CAS Google Scholar
  8. Sette, A. et al. Antigen analogs/MHC complexes as specific T cell receptor antagonists. Annu. Rev. Immun. 12, 413 (1994).
    Article CAS Google Scholar
  9. Rock, K.L., Rothstein, L., Gamble, S. & Fleischacker, F. Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules. J. Immun. 150, 438–446 (1993).
    CAS PubMed Google Scholar
  10. Kovacsovics-Bankowski, M. & Rock, K.L. A phagosome-to-cytosol pathway for ex-ogenous antigens presented on MHC class I molecules. Science 267, 243–246 (1995).
    Article CAS Google Scholar
  11. Levitski, H.I., Lazenby, A., Hayashi, R.J. & Pardoll, D.M. In vivo priming of two distinct anti tumor effectors populations: The role of MHC class I expression. J. exp. Med. 179, 1215–1224 (1994).
    Article Google Scholar
  12. Kunding, T.M. et al. Fibroblasts as efficient antigen-presenting _Cell_s in lymphoid organs. Science 268, 1343–1346 (1995).
    Article Google Scholar
  13. Kast, W.M., Brandt, R.M. & Melief, C.J. Strict peptide length is not required for the induction of cytotoxic T lymphocyte-mediated anti viral protection by peptide vaccination. Eur. J. Immun. 23, 1189–1192 (1993).
    Article CAS Google Scholar
  14. Schultz, M., Zingernagel, R.M. & Hengarther, H. Peptide-induced anti viral protection by cytotoxic T cells. Proc. natn. Acad. Sci. U.S.A. 88, 991–993 (1991).
    Article Google Scholar
  15. North, R.J. & Awwad, M. Elimination of cycling CD4+ suppressor T cells with an anti-mitotic drug releases non-cycling CD8+ T cells to cause regression of an advanced lymphoma. Immunol. 71, 90–95 (1990).
    CAS Google Scholar
  16. Rakmilevich, A.L. & North, R.J. Elimination of CD4+ T cells in mice bearing advanced sarcoma augments the anti tumor action of interleukin-2. Cancer Immun. Immunother. 38, 197–112 (1994).
    Google Scholar
  17. Rakmilevich, A.L. & North, R.J. & Dye, E.S. Presence of CD4+ T suppressor cells in mice endeared unresponsive to tumor antigens by intravenous injection of irradiated tumor cells. Int. J. Cancer. 53, 338–343 (1993).
    Article Google Scholar
  18. Awwad, M. & North, R.J. Cydopohsphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: A consequence of eliminating precursor L3T4+ suppressor T-cells. Cancer Res. 49, 1649–1654 (1989).
    CAS PubMed Google Scholar
  19. Gelber, C., Eisenbach, L., Feldman, M. & Goodenow, R.S. T-cell subset analysis of Lewis lung carcinoma tumor rejection: Heterogeneity of effectors and evidence for negative regulatory lymphocytes correlating with metastasis. Cancer Res. 52, 6507–6515 (1992).
    CAS PubMed Google Scholar
  20. Powrie, F. & Coffman, R.L. Cytokine regulation of T-cell function: Potential for therapeutic intervention. Immun. Today 14, 270–273 (1993).
    Article CAS Google Scholar
  21. Feltkamp, M.C.W. et al. Vaccination with cytotoxic T lymphocyte epitope-contaning peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur. J. Immun. 23, 2242–2249 (1993).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel
    Ofer Mandelboim, Ezra Vadai, Anne Katz-Hillel, Michael Feldman, Gideon Berke & Lea Eisenbach
  2. Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel
    Mati Fridkin

Authors

  1. Ofer Mandelboim
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  2. Ezra Vadai
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  3. Mati Fridkin
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  4. Anne Katz-Hillel
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  5. Michael Feldman
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  6. Gideon Berke
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  7. Lea Eisenbach
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Mandelboim, O., Vadai, E., Fridkin, M. et al. Regression of established murine carcinoma metastases following vaccination with tumour-associated antigen peptides.Nat Med 1, 1179–1183 (1995). https://doi.org/10.1038/nm1195-1179

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