Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

• Published in: Cancer Immunology, Immunotherapy Vol. 60; no. 11; pp. 1553 - 1564
• Main Authors: Hunger, Robert E., Kernland Lang, Kristin, Markowski, Carrie J., Trachsel, Sissel, Møller, Mona, Eriksen, Jon A., Rasmussen, Anne-Marie, Braathen, Lasse R., Gaudernack, Gustav
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2011; Springer; Springer Nature B.V
• Subjects: Adjuvants; Adult; Aged; Amino Acid Sequence; Antigens; Antineoplastic agents; Biological and medical sciences; Cancer Research; Cancer therapies; Cancer vaccines; Cancer Vaccines - adverse effects; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Cell proliferation; Chemotherapy; Clinical trials; Cytotoxicity; Dermatology; Disease; Female; Granulocyte-macrophage colony-stimulating factor; Histocompatibility antigen HLA; Humans; Hypersensitivity (delayed); Immunology; Immunotherapy; Lymphocytes; Lymphocytes T; Male; Medical sciences; Medicine; Medicine & Public Health; Melanoma; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Middle Aged; Molecular Sequence Data; Oncology; Original; Original Article; Patients; Peptide Fragments - adverse effects; Peptide Fragments - immunology; Peptide Fragments - therapeutic use; Peptides; Pharmacology. Drug treatments; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Telomerase; Telomerase - adverse effects; Telomerase - immunology; Telomerase - therapeutic use; telomerase reverse transcriptase; Tissue typing; Tuberculin; Tumor cell lines; Tumors of the skin and soft tissue. Premalignant lesions; Vaccination; Vaccines; Norway; hTERT; Telomerase; Vaccination; Immunotherapy; Melanoma; Cytotoxic T cells; Human; Catalytic subunit; Skin disease; Peptides; Enzyme; Patient; Malignant tumor; Skin cancer; Prevention; Treatment; Malignant melanoma; Cytotoxic T lymphocyte; Cancer
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-011-1061-z

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 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole 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.