Immunological evaluation of neoadjuvant peptide vaccination before radical prostatectomy for patients with localized prostate cancer.
BACKGROUND
The purpose of this study was to determine the safety and immune responses of pre-operative personalized peptide vaccine for patients with localized prostate cancer.


METHODS
Ten human leukocyte antigen (HLA)-A24(+) patients with localized prostate cancer received weekly personalized peptide vaccine for six times with positive peptides (up to four kinds of peptides) from 16 kinds of vaccine candidates, followed by a retropubic radical prostatectomy (RRP). Eight patients with localized prostate cancer receiving RRP served as the control group. The serum prostate-specific antigen (PSA) level, and peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production, and peptide-reactive immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay were monitored during the treatment. Distributions of CD45RO(+) cells, CD8(+) T cells, and CD20(+) B cells in tissue microarray samples were studied using an immunohistochemical technique.


RESULTS
The peptide vaccination was safe and well tolerated with no major adverse effects. Increased CTL response and the anti-peptide IgG titer were observed in the post-vaccination samples in 8 of 10 or 8 of 10 patients, respectively. The intensity of CD45RO(+) infiltrating cells in the vaccination group was significantly larger than that in the control group. CD8(+) T cell infiltration was seen only in the vaccinated group.


CONCLUSIONS
Increased immune responses, at both the circulation and tumor sites in the vaccinated group, support the further development of personalized peptide vaccines for patients with localized prostate cancer.
Noguchi
Masanori
M
Department of Urology, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp
Yao
Akihisa
A
Harada
Mamoru
M
Nakashima
Osamu
O
Komohara
Yoshihiro
Y
Yamada
Satoko
S
Itoh
Kyogo
K
Matsuoka
Kei
K
D000368:Aged; D019496:Cancer Vaccines; D015234:HLA-A Antigens / Q000097:blood; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D022223:Vaccines, Subunit / Q000627:therapeutic use*
D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D017493:Leukocyte Common Antigens; D017430:Prostate-Specific Antigen