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
Urban, J.L. & Schreiber, H. Tumor antigens. Annu. Rev. Immun. 10, 617–644 (1992).
Dranoff, G. et al. Vaccination with irradiated tumor Cells 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).
Melief, C.J. Tumor eradication by adoptive transfer of cytotoxic T lymphocytes. Adv. Cancer Res. 58, 143–175 (1992).
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).
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).
Mandelboim, O. et al. CTL induction by a tumor associated antigen octapeptide derived from a murine lung carcinoma Nature 369, 67–71 (1994).
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).
Sette, A. et al. Antigen analogs/MHC complexes as specific T cell receptor antagonists. Annu. Rev. Immun. 12, 413 (1994).
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).
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).
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).
Kunding, T.M. et al. Fibroblasts as efficient antigen-presenting Cells in lymphoid organs. Science 268, 1343–1346 (1995).
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).
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).
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).
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).
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).
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).
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).
Powrie, F. & Coffman, R.L. Cytokine regulation of T-cell function: Potential for therapeutic intervention. Immun. Today 14, 270–273 (1993).
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).
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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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DOI: https://doi.org/10.1038/nm1195-1179
