Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma.
Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma.
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DOI：
10.1007/s00262-016-1890-x
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发表时间：
2016-11
影响因子：
5.8
通讯作者：
Hutson, Alan D.
中科院分区：
文献类型：
--
作者：
Fenstermaker, Robert A.;Ciesielski, Michael J.;Qiu, Jingxin;Yang, Nuo;Frank, Cheryl L.;Lee, Kelvin P.;Mechtler, Laszlo R.;Belal, Ahmed;Ahluwalia, Manmeet S.;Hutson, Alan D.
Survivin是一种抗凋亡蛋白，在许多癌症中高度表达，包括恶性胶质瘤。临床前研究证实，缀合的存活素肽模拟物SurVaxM（SVN 53 -67/M57-KLH）可以刺激针对鼠胶质瘤的体内抗肿瘤免疫应答，以及离体人胶质瘤细胞。本临床研究旨在检测疫苗的安全性、免疫原性和临床效果。复发恶性胶质瘤患者，其肿瘤为存活素阳性，并且具有HLA-A*02或HLA-A*03 MHC I类等位基因阳性，以2周间隔皮下注射溶于Montanide伊萨51的SurVaxM（500 μg）和沙格司亭（100 μg）。SurVaxM耐受性良好，大多数为1级不良事件（AE），没有可归因于研究药物的严重不良事件（SAE）。6例患者发生局部注射部位反应; 3例患者报告疲乏（1级和2级），2例患者发生肌痛（1级）。8例免疫学可评价的患者中有6例对疫苗产生了细胞和体液免疫应答。该疫苗还刺激HLA-A*02、HLA-A*03和HLA-A*24限制性T细胞应答。3例患者维持部分临床应答或疾病稳定超过6个月。中位无进展生存期为17.6周，中位总生存期为86.6周，9例患者中有7例存活超过12个月。
Survivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurVaxM (500 μg) in Montanide ISA 51 with sargramostim (100 μg) at 2-week intervals. SurVaxM was well tolerated with mostly grade one adverse events (AE) and no serious adverse events (SAE) attributable to the study drug. Six patients experienced local injection site reactions; three patients reported fatigue (grades 1 and 2), and 2 patients experienced myalgia (grade 1). Six of eight immunologically evaluable patients developed both cellular and humoral immune responses to vaccine. The vaccine also stimulated HLA-A*02, HLA-A*03 and HLA-A*24 restricted T cell responses. Three patients maintained a partial clinical response or stable disease for more than 6 months. Median progression-free survival was 17.6 weeks, and median overall survival was 86.6 weeks from study entry with seven of nine patients surviving more than 12 months.
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DOI：
10.1084/jem.188.12.2357
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung K;Hayashi R;Lafond-Walker A;Lowenstein C;Pardoll D;Levitsky H
通讯作者：
Levitsky H
影响因子：
7.2
作者：
Muller, Laurent;Muller-Haegele, Sylvia;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
影响因子：
11.2
作者：
Moeller, Maria;Kershaw, Michael H.;Darcy, Phillip K.
通讯作者：
Darcy, Phillip K.
影响因子：
5.8
作者：
Ciesielski, Michael J.;Apfel, Lisa;Fenstermaker, Robert A.
通讯作者：
Fenstermaker, Robert A.
影响因子：
10.1
作者：
Shen L;Sundstedt A;Ciesielski M;Miles KM;Celander M;Adelaiye R;Orillion A;Ciamporcero E;Ramakrishnan S;Ellis L;Fenstermaker R;Abrams SI;Eriksson H;Leanderson T;Olsson A;Pili R
通讯作者：
Pili R