Approaches to dendritic cell-based immunotherapy after peripheral blood stem cell transplantation.
High-dose chemotherapy with peripheral blood progenitor cell transplantation (PBPCT) is a potentially curative treatment option for patients with both hematological malignancies and solid tumors, including breast cancer. However, based on a number of clinical studies, there is strong evidence that minimal residual disease (MRD) persists after high-dose chemotherapy in a number of patients, which eventually results in disease recurrence. Therefore, several approaches to the treatment of MRD are currently being evaluated, including treatment with dendritic cell (DC)-based cancer vaccines. DCs, which play a crucial role with regard to the initiation of T-lymphocyte responses, can be generated ex vivo either from CD34+ hematopoietic progenitor cells or from blood monocytes. They can be pulsed in vitro with tumor-derived peptides or proteins, and then used as a professional antigen-presenting cell (APC) vaccine for the induction of antigen-specific T-lymphocytes in vivo. This paper summarizes our preclinical studies on the induction of primary HER-2/neu specific cytotoxic T-lymphocyte (CTL) responses using peptide-pulsed DC. As HER-2/neu is overexpressed on 30-40% of breast and ovarian cancer cells, this novel vaccination approach might be particularly applicable to advanced breast or ovarian cancer patients after high-dose chemotherapy and autologous PBPCT.
Brugger
W
W
University of Tübingen, Medical Center II, Department of Hematology, Oncology, Immunology, and Rheumatology, Germany.
Brossart
P
P
Scheding
S
S
Stuhler
G
G
Heinrich
K
K
Reichardt
V
V
Grünebach
F
F
Bühring
H J
HJ
Kanz
L
L
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D019496:Cancer Vaccines; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D018365:Neoplasm, Residual / Q000276:immunology / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D018952:Antigens, CD34; D019496:Cancer Vaccines