Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.
Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.
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DOI：
10.1186/1479-5876-11-246
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发表时间：
2013-10-05
影响因子：
7.4
通讯作者：
Shiku H
中科院分区：
文献类型：
--
作者：
Kageyama S;Wada H;Muro K;Niwa Y;Ueda S;Miyata H;Takiguchi S;Sugino SH;Miyahara Y;Ikeda H;Imai N;Sato E;Yamada T;Osako M;Ohnishi M;Harada N;Hishida T;Doki Y;Shiku H
胆固醇普鲁兰（CHP）是一种新型的肿瘤疫苗抗原递送系统。本研究评估了接受CHP-NY-ESO-1复合疫苗（药物代码：IMF-001）的患者的安全性、免疫反应和临床结果。招募晚期/转移性食管癌患者，皮下接种100 μg或200 μg的NY-ESO-1蛋白复合物CHP。主要终点是安全性和体液免疫应答，次要终点是临床疗效。共有25名患者入组。13例和12例患者分别重复接种100 μg和200 μg的CHP-NY-ESO-1，中位剂量分别为8剂和9.5剂。未观察到与疫苗相关的严重不良事件。100 μg组13例患者中有3例基线时抗ny - eso -1抗体阳性，200 μg组12例患者中有7例基线时抗体阳性。在100 μg的队列中，10例抗体前阴性患者中有5例出现抗体应答，2例抗体前阳性患者接种疫苗后抗体水平增强。在200 μg的队列中，抗体前阴性的5例患者全部变为血清阳性，抗体前阳性的7例患者抗体水平全部扩增。未见肿瘤缩小。接受200 μg CHP-NY-ESO-1治疗的患者比接受100 μg CHP-NY-ESO-1治疗的患者存活时间更长，即使那些对先前治疗无反应或肿瘤负担更高的患者也是如此。证实了CHP-NY-ESO-1疫苗的安全性和免疫原性。200 μg剂量更有效地诱导免疫反应，并显示更好的生存效益。（临床试验注册号NCT01003808）。
Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001. Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy. A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens. The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).
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影响因子：
20.3
作者：
Ikuta, Y;Katayama, N;Shiku, H
通讯作者：
Shiku, H
影响因子：
6.4
作者：
Kawabata, Ryohei;Wada, Hisashi;Nakayama, Eiichi
通讯作者：
Nakayama, Eiichi
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1073/pnas.94.5.1914
发表时间：
1997-03-04
影响因子：
11.1
作者：
Chen, YT;Scanlan, MJ;Old, LJ
通讯作者：
Old, LJ
影响因子：
45.3
作者：
Small, Eric J.;Schellhammer, Paul F.;Hershberg, Robert M.
通讯作者：
Hershberg, Robert M.