Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination.
BACKGROUND
To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted.


METHODS
This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides.


RESULTS
Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions.


CONCLUSIONS
Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer.
Noguchi
Masanori
M
Department of Urology, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp
Kobayashi
Kazuhiko
K
Suetsugu
Norie
N
Tomiyasu
Katsurou
K
Suekane
Shigetaka
S
Yamada
Akira
A
Itoh
Kyogo
K
Noda
Shinshi
S
D000230:Adenocarcinoma / Q000737:chemistry / Q000276:immunology* / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D004268:DNA-Binding Proteins / Q000032:analysis; D015234:HLA-A Antigens / Q000032:analysis; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000628:therapy*; D016601:RNA-Binding Proteins / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C416530:SART3 protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017430:Prostate-Specific Antigen; C405383:DSE protein, human