Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.
BACKGROUND
Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer.


METHODS
A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively).


RESULTS
No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA.


CONCLUSIONS
Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.
Murphy
G
G
Pacific Northwest Cancer Foundation, Cancer Research Division, Northwest Hospital, Seattle, Washington 98125, USA.
Tjoa
B
B
Ragde
H
H
Kenny
G
G
Boynton
A
A
D003713:Dendritic Cells / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D015234:HLA-A Antigens / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007022:Hypotension / Q000453:epidemiology / Q000503:physiopathology; D007150:Immunohistochemistry; D015994:Incidence; D016898:Interferon-alpha / Q000097:blood; D008297:Male; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000032:analysis* / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015234:HLA-A Antigens; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D017430:Prostate-Specific Antigen