Suzuki Hiroyuki, Fukuhara Mitsuro, Yamaura Takumi, Mutoh Satoshi, Okabe Naoyuki, Yaginuma Hiroshi, Hasegawa Takeo, Yonechi Atsushi, Osugi Jun, Hoshino Mika, Kimura Takashi, Higuchi Mitsunori, Shio Yutaka, Ise Kazuya, Takeda Kazuyoshi, Gotoh Mitsukazu
J Transl Med. 2013 Apr 11;11:97. doi: 10.1186/1479-5876-11-97.
Vaccine treatment using multiple peptides derived from multiple proteins is considered to be a promising option for cancer immune therapy, but scientific evidence supporting the therapeutic efficacy of multiple peptides is limited.
We conducted phase I trials using a mixture of multiple therapeutic peptide vaccines to evaluate their safety, immunogenicity and clinical response in patients with advanced/recurrent NSCLC. We administered two different combinations of four HLA-A24-restricted peptides. Two were peptides derived from vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2), and the third was a peptide derived from up-regulated lung cancer 10 (URLC10, which is also called lymphocyte antigen 6 complex locus K [LY6K]). The fourth peptide used was derived from TTK protein kinase (TTK) or cell division associated 1 (CDCA1). Vaccines were administered weekly by subcutaneous injection into the axillary region of patients with montanide ISA-51 incomplete Freund's adjuvant, until the disease was judged to have progressed or patients requested to be withdrawn from the trial. Immunological responses were primarily evaluated using an IFN-gamma ELiSPOT assay.
Vaccinations were well tolerated with no severe treatment-associated adverse events except for the reactions that occurred at the injection sites. Peptide-specific T cell responses against at least one peptide were observed in 13 of the 15 patients enrolled. Although no patient exhibited complete or partial responses, seven patients (47%) had stable disease for at least 2 months. The median overall survival time was 398 days, and the 1- and 2-year survival rates were 58.3% and 32.8%, respectively.
Peptide vaccine therapy using a mixture of four novel peptides was found to be safe, and is expected to induce strong specific T cell responses.
These studies were registered with ClinicalTrials.gov NCT00633724 and NCT00874588.
使用源自多种蛋白质的多种肽进行疫苗治疗被认为是癌症免疫治疗的一个有前景的选择，但支持多种肽治疗效果的科学证据有限。
我们使用多种治疗性肽疫苗混合物进行了I期试验，以评估其在晚期/复发性非小细胞肺癌患者中的安全性、免疫原性和临床反应。我们给予了两种不同组合的四种HLA - A24限制性肽。其中两种是源自血管内皮生长因子受体1（VEGFR1）和2（VEGFR2）的肽，第三种是源自上调肺癌10（URLC10，也称为淋巴细胞抗原6复合物基因座K [LY6K]）的肽。使用的第四种肽源自TTK蛋白激酶（TTK）或细胞分裂相关1（CDCA1）。通过皮下注射将疫苗每周一次注射到使用蒙旦蜡ISA - 51不完全弗氏佐剂的患者腋窝区域，直至疾病被判定进展或患者要求退出试验。免疫反应主要使用IFN - γ酶联免疫斑点分析进行评估。
疫苗接种耐受性良好，除注射部位出现的反应外，无严重的治疗相关不良事件。在纳入的所有15名患者中，有13名观察到针对至少一种肽的肽特异性T细胞反应。虽然没有患者表现出完全或部分缓解，但7名患者（47%）疾病稳定至少2个月。总生存时间中位数为398天，1年和2年生存率分别为58.3%和32.8%。
发现使用四种新型肽混合物的肽疫苗治疗是安全的，并有望诱导强烈的特异性T细胞反应。
这些研究已在ClinicalTrials.gov上注册，注册号为NCT00633724和NCT00874588。
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