Immunological evaluation of neoadjuvant peptide vaccination before radical prostatectomy for patients with localized prostate cancer
Immunological evaluation of neoadjuvant peptide vaccination before radical prostatectomy for patients with localized prostate cancer
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DOI：
10.1002/pros.20572
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发表时间：
2007-06-15
期刊：
影响因子：
2.8
通讯作者：
Matsuoka, Kei
中科院分区：
文献类型：
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作者：
Noguchi, Masanori;Yao, Akihisa;Matsuoka, Kei
背景本研究的目的是确定术前个体化肽疫苗用于局限性前列腺癌患者的安全性和免疫应答。10例HLA-A24（+）局限性前列腺癌患者接受了每周一次的个性化肽疫苗接种，共接种6次，从16种候选疫苗中筛选出阳性肽（最多4种肽），随后进行耻骨后根治性前列腺癌切除术（RRP）。8例局限性前列腺癌患者接受RRP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产生的肽特异性细胞毒性T淋巴细胞（CTL）前体分析和使用酶联免疫吸附测定的肽反应性免疫球蛋白G（IgG）。采用免疫组化技术研究了组织芯片样本中CD 45 RO（+）细胞、CD 8（+）T细胞和CD 20（+）B细胞的分布。肽疫苗接种是安全的，耐受性良好，没有重大的不良反应。在10名患者中的8名或10名患者中的8名中分别在接种后样品中观察到CTL应答和抗肽IgG滴度增加。免疫组CD 45 RO（+）细胞浸润强度明显大于对照组。CD 8（+）T细胞浸润仅见于免疫组。在接种组中，在循环和肿瘤部位的免疫应答增加，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。
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-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.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.