Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.
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.
Lienard
Danielle
D
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, CH-1011 Lausanne, Switzerland.
Avril
Marie-Françoise
MF
Le Gal
Frédérique-Anne
FA
Baumgaertner
Petra
P
Vermeulen
Wim
W
Blom
Astrid
A
Geldhof
Christine
C
Rimoldi
Donata
D
Pagliusi
Sonia
S
Romero
Pedro
P
Dietrich
Pierre-Yves
PY
Corvaia
Nathalie
N
Speiser
Daniel E
DE
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines; D005260:Female; D015234:HLA-A Antigens / Q000378:metabolism*; D015789:HLA-A2 Antigen; D006801:Humans; D007711:Klebsiella pneumoniae / Q000276:immunology*; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000008:administration & dosage; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C078167:OMPA outer membrane proteins