A Phase I Study of Personalized Peptide Vaccination Using 14 Kinds of Vaccine in Combination With Low-Dose Estramustine in HLA-A24-Positive Patients With Castration-Resistant Prostate Cancer
A Phase I Study of Personalized Peptide Vaccination Using 14 Kinds of Vaccine in Combination With Low-Dose Estramustine in HLA-A24-Positive Patients With Castration-Resistant Prostate Cancer
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DOI：
10.1002/pros.21261
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发表时间：
2011-04-01
期刊：
影响因子：
2.8
通讯作者：
Itoh, Kyogo
中科院分区：
文献类型：
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作者：
Noguchi, Masanori;Uemura, Hirotsugu;Itoh, Kyogo
背景评价个性化肽疫苗（PPV）联合磷酸雌莫司汀（EMP）治疗去势抵抗性前列腺癌（CRPC）的安全性、耐受性、免疫应答和抗肿瘤活性。在I期剂量递增研究中，每周以三种不同的剂量设置皮下注射显示针对14种候选疫苗（ITK-1）的肽特异性免疫球蛋白G（IgG）的最高水平的四种肽（每种肽1、3和5 mg）用低剂量EMP治疗6周，随访期最长2年，每周或每2周6次PPV为1个疗程。15例患者入组I期研究。未观察到严重的治疗相关不良事件。最常见的不良事件是注射部位的2级皮肤反应。ITK-1的最大可接受剂量为8.643 mg。没有3级或以上的治疗相关全身不良事件，并且无法确定最大耐受剂量。通过γ-干扰素释放试验测定的细胞毒性T淋巴细胞应答在15例患者中的10例（67%）中增强，IgG应答在15例患者中的7例（47%）中增强。12例患者进入扩展研究，中位生存时间为23.8个月，中位随访时间为23.8个月。PPV治疗HLA-A24阳性CRPC患者可推荐用于进一步的临床试验阶段，因为其安全性和更高的免疫应答增强频率。前列腺71：470-479，2011年。(C)2010 Wiley-Liss，Inc.
BACKGROUND. To evaluate the safety, tolerability, immune response, and antitumor activity of a combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) in patients with castration-resistant prostate cancer (CRPC).METHODS. In a phase I dose-escalation study, four peptides showing the highest levels of peptide-specific immunoglobulin G(IgG) to 14 vaccine candidates (ITK-1) were subcutaneously injected every week in three different dose settings (1, 3, and 5 mg per peptide) for 6 weeks with a low dose of EMP, and the patients were followed by maximum 2 years extension study either weekly or bi-weekly six times PPV as one course with a low dose of EMP.RESULTS. Fifteen patients were enrolled in the phase I study. No serious treatment-related adverse events were observed. The most common adverse events were grade 2 skin reactions at the injection sites. The maximum acceptable dose of ITK-1 was 8.643 mg. There were no treatment-related systemic adverse events of grade 3 or more, and maximum tolerated dose could not be determined. Cytotoxic T lymphocyte responses measured by interferon-gamma release assay were boosted in 10 of 15 (67%) patients, and IgG responses were boosted in 7 of 15 (47%) patients. Twelve patients proceeded to the extension study, and the median survival time was 23.8 months during a median follow-up of 23.8 months.CONCLUSIONS. PPV treatment for HLA-A24 positive patients with CRPC could be recommended for further stages of clinical trials because of its safety and the higher frequency of boosting immune responses. Prostate 71: 470-479, 2011. (C) 2010 Wiley-Liss, Inc.