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Phase I/II study of immunotherapy with T-cell peptide epitopes in patients with stage IV melanoma

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Abstract

Previous studies in small groups of patients suggested that immunization of melanoma patients with peptide epitopes recognized by T cells could induce regression of melanoma. This approach was tested in 36 patients with stage IV melanoma. The (MHC class I–restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3. The gp100 and MART-1 peptides had been modified to increase their immunogenicity. In half the patients (groups 3 and 4) the peptides were given in the adjuvant Montanide-ISA-720, and half the patients in both groups were given GM-CSF s.c. for 4 days following each injection. Treatment was well tolerated except for two severe erythematous responses to Montanide-ISA-720 and marked inflammatory responses at sites of GM-CSF administration in three patients. There were no objective clinical responses but stabilization of disease for periods from 3 to 12 months were seen in seven patients. Five of these were patients given the peptides in Montanide-ISA-720. Delayed-type hypersensitivity (DTH) skin test responses were also seen mainly in the patients given the peptides in Montanide-ISA-720. GM-CSF did not increase DTH responses in patients in the latter group but may have increased DTH responses in those not given peptides in Montanide-ISA-720. Inflammatory responses around s.c. metastases or regional lymph nodes were observed in two patients. These results suggest that the peptides are more effective when given in the adjuvant Montanide-ISA-720. Nevertheless, results from this study, together with those from a number of comparable studies, indicate that peptide vaccines are currently of minimal benefit to patients and support the need for ongoing development of new strategies in treatment of this disease.

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia and in part by the Sydney Melanoma Foundation and the Hunter Melanoma Foundation.

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Authors and Affiliations

  1. Oncology and Immunology Unit, Room 443, David Maddison Clinical Sciences Building, King & Watt Streets, Newcastle, NSW, 2300, Australia

    Peter Hersey, Tam Nguyen & Margaret Farrelly

  2. Sydney Melanoma Unit, Royal Prince Alfred Hospital, Level 3, Gloucester House, Camperdown, NSW, 2050, Australia

    Scott W. Menzies, Debbie Hirst & Heather Johnson

  3. Adelaide Melanoma Unit, Department of Surgery, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide, SA, 5000, Australia

    Brendon Coventry

  4. Newcastle Melanoma Unit, Newcastle Mater Hospital, Edith Street, Waratah, NSW, 2298, Australia

    Susan Collins

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  1. Peter Hersey
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Correspondence to Peter Hersey.

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Hersey, P., Menzies, S.W., Coventry, B. et al. Phase I/II study of immunotherapy with T-cell peptide epitopes in patients with stage IV melanoma. Cancer Immunol Immunother 54, 208–218 (2005). https://doi.org/10.1007/s00262-004-0587-8

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