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Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant

Lienard, Danielle
Avril, Marie-Françoise
Baumgaertner, Petra
Vermeulen, Wim
Blom, Astrid
Geldhof, Christine
Rimoldi, Donata
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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 & dosageAdultAgedAged, 80 and overAntigens, Neoplasm/administration & dosageBacterial Outer Membrane Proteins/administration & dosageCD8-Positive T-Lymphocytes/*metabolism/pathology*Cancer VaccinesFemaleHLA-A Antigens/*metabolismHLA-A2 AntigenHumansKlebsiella pneumoniae/*immunologyMART-1 AntigenMaleMelanoma/*immunology/pathology/physiopathology/*therapyMiddle AgedNeoplasm Proteins/administration & dosageNeoplasm StagingPeptide Fragments/administration & dosageSkin Neoplasms/*immunology/pathology/physiopathology/*therapy
PMID: 19752746
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Research group Immunothérapie des cancers (42)
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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

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Deposited on : 2012-04-23

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