Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity.
Dendritic cells (DCs) are "professional" antigen-presenting cells capable of stimulating T-cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T-cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA-restricted fashion in order to stimulate T-cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.
Pacific Northwest Cancer Foundation, Northwest Hospital, Seattle, Washington 98125, USA.
B
B
Tjoa
A
A
Boynton
G
G
Kenny
H
H
Ragde
S L
SL
Misrock
G
G
Murphy
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D043425:Glutamate Carboxypeptidase II; D015234:HLA-A Antigens; D006801:Humans; D016233:Immunotherapy, Active; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015234:HLA-A Antigens; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II