Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination
Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination
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DOI：
10.1002/pros.10276
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发表时间：
2003-09-15
期刊：
影响因子：
2.8
通讯作者：
Noda, S
中科院分区：
文献类型：
--
作者：
Noguchi, M;Kobayashi, K;Noda, S
背景。为了评估基于肽的免疫疗法对激素难治性前列腺癌患者的安全性和免疫反应，进行了 I 期临床试验。本研究首先调查了 10 名激素难治性前列腺癌患者的疫苗接种前外周血单核细胞 (PBMC) 中是否可检测到与候选疫苗肽（HLA-A24 阳性患者的 14 种肽）反应的细胞毒性 T 淋巴细胞 (CTL) 前体。然后对患者进行皮下疫苗接种，仅使用与疫苗接种前 PBMC 发生反应的肽（CTL 前体导向肽疫苗），最多可接种四种肽。结果。总体而言，疫苗接种的耐受性良好，但大多数患者（十分之九）在注射部位出现 1 级局部红肿。在 10 名患者中有 4 名观察到 CTL 对肽和癌细胞的反应增加。十名患者中有七名的疫苗接种后血清中也检测到了抗肽 IgG 抗体。一名患者取得了部分缓解，PSA 下降了 89%。 10 名患者中有 5 名 (50%) 病情稳定，中位持续时间为 2 个月（范围为 2-5 个月）。没有可测量病变的客观反应。结论。一些患者细胞和体液免疫反应的增加以及 PSA 水平的降低支持进一步开发基于肽的免疫疗法来治疗激素难治性前列腺癌。 (C) 2003 Wiley-Liss, Inc.
BACKGROUND. To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted.METHODS. This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides.RESULTS. Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions.CONCLUSIONS. Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer. (C) 2003 Wiley-Liss, Inc.