Yutani Shigeru, Komatsu Nobukazu, Shichijo Shigeki, Yoshida Kazumi, Takedatsu Hiroko, Itou Minoru, Kuromatu Ryoko, Ide Tatsuya, Tanaka Masatoshi, Sata Michio, Yamada Akira, Itoh Kyogo
Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Cancer Sci. 2009 Oct;100(10):1935-42. doi: 10.1111/j.1349-7006.2009.01256.x. Epub 2009 Jun 23.
Hepatitis C virus (HCV) infection has a high risk of liver cirrhosis and hepatocellular carcinoma at later stages. We recently identified a peptide derived from the HCV core protein capable of inducing both cellular and humoral responses to nearly all HCV-positive patients in Japan with different human leukocyte antigen (HLA)-class I-A alleles. To assess the safety and immune responses to this novel peptide, we conducted a phase I dose-escalation study of the vaccination for 26 HCV-positive patients who were either non-responders to the interferon-based therapy (n = 23) or refused it (n = 3). The regimen was well tolerated, with no severe vaccine-related toxicity. Twenty-five and 22 patients completed the first and second cycle vaccination (6 and 12 vaccine injections), respectively. After a series of six vaccine injections, peptide-specific CTL activity was augmented in peripheral blood mononuclear cells from 15 of 25 patient samples, with an expected optimal dose of 1 mg peptide. After 12 vaccine injections, peptide-specific IgG production was augmented in plasma from the majority of patients (15 of 22 patients) tested, but not in a dose-dependent fashion. There were two HCV RNA responders with >1 log declines. Among patients whose pre-vaccination levels of alanine aminotransferase and alpha feto-protein exceeded the normal ranges, a <30% decrease was found in 7 of 24 and three of six patients, respectively. Because of its tolerability and higher rate of immune boosting, this protocol is recommended for a phase II study to investigate its clinical efficacy.
丙型肝炎病毒（HCV）感染在后期有很高的肝硬化和肝细胞癌风险。我们最近鉴定出一种源自HCV核心蛋白的肽，它能够在日本几乎所有具有不同人类白细胞抗原（HLA）-I类A等位基因的HCV阳性患者中诱导细胞免疫和体液免疫反应。为了评估对这种新型肽的安全性和免疫反应，我们对26例HCV阳性患者进行了疫苗接种的I期剂量递增研究，这些患者要么是对基于干扰素的治疗无反应者（n = 23），要么是拒绝接受该治疗者（n = 3）。该方案耐受性良好，没有严重的疫苗相关毒性。25例和22例患者分别完成了第一和第二周期的疫苗接种（6次和12次疫苗注射）。在进行了一系列6次疫苗注射后，25份患者样本中的15份外周血单个核细胞中的肽特异性CTL活性增强，预期最佳剂量为1mg肽。在进行12次疫苗注射后，大多数接受检测的患者（22例中的15例）血浆中的肽特异性IgG产生增加，但并非呈剂量依赖性。有2例HCV RNA应答者病毒载量下降超过1个对数。在接种疫苗前丙氨酸转氨酶和甲胎蛋白水平超过正常范围的患者中，24例中的7例和6例中的3例分别出现了<30%的下降。由于其耐受性和较高的免疫增强率，该方案推荐用于II期研究以调查其临床疗效。
