Immune monitoring in a phase 1 trial of a PSA DNA vaccine in patients with hormone-refractory prostate cancer.
Prostate cancer remains a leading cause of cancer illness and death among men in Europe. No curative treatment exists when the disease has spread beyond the prostate. Immunotherapy with DNA vaccines has emerged as a potential therapeutic approach for the induction of antitumor specific cytotoxic T lymphocytes. In this study six patients with hormone-refractory prostate cancer were monitored for their ability to mount PSA-specific cellular responses after receiving a pVAX/PSA DNA vaccine (patients 1-3, 100 microg; patients 7-9, 900 microg) with recombinant GM-CSF and IL-2 as adjuvants. IFNgamma ELISPOT showed that naturally processed PSA protein and PSA peptides are recognized by T cells in the blood of some prostate cancer patients after a PSA DNA vaccine. Analysis of other cytokines showed the production of IL-4 and IL-6 but importantly did not show an increase in the number of IL-10-producing cells after vaccination in any of the patients. The authors conclude that a pVAX/PSA DNA vaccine can induce PSA-specific cellular immune responses in patients with hormone-refractory prostate cancer, thus emphasizing the potential for PSA as a target molecule for the immunotherapy of prostate cancer.
Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska Institute, 171 76 Stockholm, Sweden. Ashley.Miller@cck.ki.se
Ashley M
AM
Miller
Volkan
V
Ozenci
Rolf
R
Kiessling
Pavel
P
Pisa
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D015166:Monitoring, Immunologic; D010446:Peptide Fragments / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D015703:Antigens, CD; D018931:Antineoplastic Agents, Hormonal; D007378:Interleukins; D010446:Peptide Fragments; D019444:Vaccines, DNA; D016753:Interleukin-10; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen