[Cell therapy and prostate cancer].
Hormonotherapy is the standard treatment for advanced prostate cancer but disease progression ineluctably occurs. Subsequent chemotherapy has a modest symptomatic palliative role even if encouraging results were recently presented with docetaxel and estramustine combination. In this context, there is a great deal of interest in using dendritic cells therapeutically, as they are the most potent professional antigen-presenting cells in the immune system. Based on their unique adjuvant capacity, two vaccinal strategies are therefore tested in clinical trials. First approach includes the administration of cancer cells transduced by a cytokine gene to stimulate the in vivo recruitment and activation of dendritic cells, and the most advanced studies use GM-CSF gene-transduced allogenic cells. The second approach consists in infusions of dendritic cells loaded ex vivo with relevant tumoral antigens. Two prostate antigens have already been used. PSMA evaluated in 130 patients and a fusion protein PAP-GM-CSF (Provenge) in 144 patients. All treatments were well tolerated and frequently generated weak specific responses, but resulted in a limited clinical efficacy. However, engineering of dendritic cells can provide optimised cell vectors able to amplify vaccine response and clinical efficacy.
Eymard
Jean-Christophe
JC
Unité fonctionnelle de recherche clinique et de thérapie cellulaire, Institut Jean-Godinot, 1. av du général Koenig, 51056 Reims, France. jc.eymard@reims.fnclcc.fr
Bernard
J
J
D000135:Acid Phosphatase / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000637:transplantation; D000954:Antigens, Surface / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002465:Cell Movement; D017321:Clinical Trials, Phase I as Topic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D043425:Glutamate Carboxypeptidase II / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D011467:Prostate / Q000201:enzymology; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000954:Antigens, Surface; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen