EGFRvIII-targeted vaccination therapy of malignant glioma.
EGFRvIII-targeted vaccination therapy of malignant glioma.
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DOI：
10.1111/j.1750-3639.2009.00318.x
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Sampson JH
中科院分区：
文献类型：
--
作者：
Choi BD;Archer GE;Mitchell DA;Heimberger AB;McLendon RE;Bigner DD;Sampson JH
鉴于恶性胶质瘤的高度浸润性生长模式和缺乏与目前可用的治疗方案相关的特异性，旨在根除癌细胞同时限制正常组织中的附带毒性的替代策略仍然是高度优先的。为此，针对靶向肿瘤细胞的特异性免疫疗法的发展代表了一种有前途的方法。表皮生长因子受体III类变体（EGFRvIII）是野生型酪氨酸激酶的组成性激活突变体，存在于相当大比例的恶性神经胶质瘤和其他人类癌症中，但在正常组织中完全不存在。该受体变体由框内缺失组成，其翻译产生具有新型甘氨酸残基的细胞外连接，所述甘氨酸残基侧接通常在正常蛋白质中不相邻的氨基酸序列。在这篇综述中，概括了针对EGFRvIII抗原结构域的这一部分的肽疫苗的临床前和早期临床开发。在接种疫苗后，我们的小组已经证明了对表达突变受体的癌细胞的有效的、重定向的细胞和体液免疫，而没有显著的毒性。此外，在这些研究中观察到的相应治疗结果证实了基于肽的疫苗接种策略在恶性胶质瘤患者中新兴的抗肿瘤免疫疗法中的潜在作用。
Given the highly infiltrative growth pattern of malignant glioma and the lack of specificity associated with currently available treatment regimens, alternative strategies designed to eradicate cancer cells while limiting collateral toxicity in normal tissues remain a high priority. To this end, the development of specific immunotherapies against targeted neoplastic cells represents a promising approach. The epidermal growth factor receptor class III variant (EGFRvIII), a constitutively activated mutant of the wild-type tyrosine kinase, is present in a substantial proportion of malignant gliomas and other human cancers, yet completely absent from normal tissues. This receptor variant consists of an in-frame deletion, the translation of which produces an extracellular junction with a novel glycine residue, flanked by amino acid sequences that are not typically adjacent in the normal protein. In this review, both preclinical and early clinical development of a peptide vaccine directed against this portion of the EGFRvIII antigenic domain are recapitulated. Following vaccination, our group has demonstrated potent, redirected cellular and humoral immunity against cancer cells expressing the mutant receptor without significant toxicity. Additionally, the corresponding therapeutic outcomes observed in these studies lend credence to the potential role of peptide-based vaccination strategies among emerging antitumor immunotherapies in patients with malignant glioma.
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影响因子：
4.8
作者：
Antonyak, MA;Moscatello, DK;Wong, AJ
通讯作者：
Wong, AJ
影响因子：
82.9
作者：
Backskai, BJ;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT
影响因子：
32.4
作者：
BOEL, P;WILDMANN, C;VANDERBRUGGEN, P
通讯作者：
VANDERBRUGGEN, P
DOI：
10.1073/pnas.151261398
发表时间：
2001-07-17
影响因子：
11.1
作者：
DeMattos, RB;Bales, KR;Holtzman, DM
通讯作者：
Holtzman, DM
影响因子：
82.9
作者：
Bard, F;Cannon, C;Yednock, T
通讯作者：
Yednock, T