Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

Autor: Carrie J. Markowski, Lasse R. Braathen, Gustav Gaudernack, Kristin Kernland Lang, Mona Møller, Anne Marie Rasmussen, Jon Alm Eriksen, Sissel Trachsel, Robert E. Hunger
Rok vydání: 2011
Předmět:
Zdroj: Hunger, Robert E; Kernland Lang, Kristin; Markowski, Carrie J; Trachsel, Sissel; Møller, Mona; Eriksen, Jon A; Rasmussen, Anne-Marie; Braathen, Lasse R; Gaudernack, Gustav (2011). Vaccination of patients with cutaneous melanoma with telomerase-specific peptides. Cancer immunology, immunotherapy, 60(11), pp. 1553-64. Heidelberg: Springer-Verlag 10.1007/s00262-011-1061-z
ISSN: 1432-0851
0340-7004
Popis: 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
Databáze: OpenAIRE
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