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Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant |
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Published in | Journal of Immunotherapy. 2009, vol. 32, no. 8, p. 875-883 | |
Abstract | Toll-like receptor ligands are potentially useful adjuvants for the development of clinical T cell vaccination. Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae. Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals. Adverse reactions were mild-to-moderate. Fourteen patients received at least 8 vaccinations and were thus evaluable for clinical tumor and immune responses. Seven patients experienced progressive disease, whereas 2 patients had stable disease throughout the trial period, 1 of them with regression of multiple skin metastases. The remaining 5 patients had no measurable disease. Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients. Increased percentages of T cells were found in three patients, memory/effector T cell differentiation in 4 patients, and a positive interferon-gamma Elispot assay in 1 patient. Antibody responses to P40 were observed in all patients. We conclude that vaccination with peptide and P40 was feasible and induced ex vivo detectable tumor antigen specific T cell responses in 6 of 14 patients with advanced melanoma. | |
Keywords | Adjuvants, Immunologic/administration & dosage — Adult — Aged — Aged, 80 and over — Antigens, Neoplasm/administration & dosage — Bacterial Outer Membrane Proteins/administration & dosage — CD8-Positive T-Lymphocytes/*metabolism/pathology — *Cancer Vaccines — Female — HLA-A Antigens/*metabolism — HLA-A2 Antigen — Humans — Klebsiella pneumoniae/*immunology — MART-1 Antigen — Male — Melanoma/*immunology/pathology/physiopathology/*therapy — Middle Aged — Neoplasm Proteins/administration & dosage — Neoplasm Staging — Peptide Fragments/administration & dosage — Skin Neoplasms/*immunology/pathology/physiopathology/*therapy | |
Identifiers | PMID: 19752746 | |
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Research group | Immunothérapie des cancers (42) | |
Citation (ISO format) | LIENARD, Danielle et al. Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant. In: Journal of Immunotherapy, 2009, vol. 32, n° 8, p. 875-883. doi: 10.1097/CJI.0b013e3181b56ad9 https://archive-ouverte.unige.ch/unige:19925 |