Immunological evaluation of neoadjuvant peptide vaccination before radical prostatectomy for patients with localized prostate cancer

• Published in: The Prostate 2007-06, Vol.67 (9), p.933-942
• Main Authors: Noguchi, Masanori, Yao, Akihisa, Harada, Mamoru, Nakashima, Osamu, Komohara, Yoshihiro, Yamada, Satoko, Itoh, Kyogo, Matsuoka, Kei
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; cancer vaccine; Cancer Vaccines; Gynecology. Andrology. Obstetrics; HLA-A Antigens - blood; HLA-A24 Antigen; Humans; Immunoglobulin G - blood; Immunohistochemistry; immunotherapy; Leukocyte Common Antigens - blood; Lymphocyte Count; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Staging; Nephrology. Urinary tract diseases; prostate cancer; Prostate-Specific Antigen - blood; Prostatectomy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; T cell; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vaccines, Subunit - therapeutic use
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20572

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. METHOD 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‐γ 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. RESULT 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. CONCLUSION 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. Prostate 67: 933–942, 2007. © 2007 Wiley‐Liss, Inc.