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

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.

• Authors: Danielle Lienard, Marie-Françoise Avril, Frédérique-Anne Le Gal, Petra Baumgaertner, Wim Vermeulen, Astrid Blom, Christine Geldhof, Donata Rimoldi, Sonia Pagliusi, Pedro Romero, Pierre-Yves Dietrich, Nathalie Corvaia, Daniel E Speiser
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 32 Issue 8 Pg. 875-83 (Oct 2009) ISSN: 1537-4513 [Electronic] United States
• PMID: 19752746 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Bacterial Outer Membrane Proteins
• Cancer Vaccines
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• MART-1 Antigen
• MLANA protein, human
• Neoplasm Proteins
• Peptide Fragments
• OMPA outer membrane proteins

Topics

• 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)