Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells.
Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-gamma staining and (51)Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu-derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.
Brossart
P
P
University of Tübingen, Department of Hematology, Oncology and Immunology, Tübingen, Germany.
Wirths
S
S
Stuhler
G
G
Reichardt
V L
VL
Kanz
L
L
Brugger
W
W
D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014182:Transplantation, Autologous; D014611:Vaccination
D018396:Mucin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C116055:MUC1 tandem repeat peptide