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Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

Hunger, Robert ; Kernland Lang, Kristin ; Markowski, Carrie ; Trachsel, Sissel ; Møller, Mona ; Eriksen, Jon ; Rasmussen, Anne-Marie ; Braathen, Lasse ; Gaudernack, Gustav

In: Cancer Immunology, Immunotherapy, 2011, vol. 60, no. 11, p. 1553-1564

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    Titel
    • Vaccination of patients with cutaneous melanoma with telomerase-specific peptides
    Autor
    • Hunger, Robert. Department of Dermatology, University of Berne, Inselspital, 3010, Berne, Switzerland
    • Kernland Lang, Kristin. Department of Dermatology, University of Berne, Inselspital, 3010, Berne, Switzerland
    • Markowski, Carrie. Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo, Norway
    • Trachsel, Sissel. Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo, Norway
    • Møller, Mona. GemVax AS, Porsgrunn, Norway
    • Eriksen, Jon. GemVax AS, Porsgrunn, Norway
    • Rasmussen, Anne-Marie. Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo, Norway
    • Braathen, Lasse. Department of Dermatology, University of Berne, Inselspital, 3010, Berne, Switzerland
    • Gaudernack, Gustav. Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo, Norway
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Cancer Immunology, Immunotherapy, 2011, vol. 60, no. 11, p. 1553-1564. Springer-Verlag
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:313429
    Summary
    Purpose: A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611-626) and p540 (hTERT: 540-548) using granulocyte-macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma. Experimental design: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8times intradermally with either 60 or 300nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated. Results: Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. Conclusion: These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials