Noguchi Masanori, Yao Akihisa, Harada Mamoru, Nakashima Osamu, Komohara Yoshihiro, Yamada Satoko, Itoh Kyogo, Matsuoka Kei
Department of Urology, Kurume University School of Medicine, Kurume, Japan.
Prostate. 2007 Jun 15;67(9):933-42. doi: 10.1002/pros.20572.
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.
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.
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.
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.
本研究旨在确定术前个性化肽疫苗用于局限性前列腺癌患者的安全性和免疫反应。
10名人类白细胞抗原（HLA）-A24（+）的局限性前列腺癌患者每周接受一次个性化肽疫苗，共6次，使用来自16种候选疫苗的阳性肽（最多4种肽），随后进行耻骨后根治性前列腺切除术（RRP）。8名接受RRP的局限性前列腺癌患者作为对照组。在治疗期间监测血清前列腺特异性抗原（PSA）水平、通过干扰素-γ产生进行的肽特异性细胞毒性T淋巴细胞（CTL）前体分析以及使用酶联免疫吸附测定法检测的肽反应性免疫球蛋白G（IgG）。使用免疫组织化学技术研究组织微阵列样本中CD45RO（+）细胞、CD8（+）T细胞和CD20（+）B细胞的分布。
肽疫苗接种安全且耐受性良好，无重大不良反应。10名患者中有8名在接种疫苗后的样本中观察到CTL反应增强，10名患者中有8名观察到抗肽IgG滴度升高。接种疫苗组中CD45RO（+）浸润细胞的强度明显大于对照组。仅在接种疫苗组中观察到CD8（+）T细胞浸润。
接种疫苗组在循环和肿瘤部位的免疫反应增强，支持进一步开发用于局限性前列腺癌患者的个性化肽疫苗。
