Generation of CTL recognizing an HLA-A*0201-restricted epitope shared by MAGE-A1,-A2,-A3,-A4,-A6,-A10, and-A12 tumor antigens: Implication in a broad-spectrum tumor immunotherapy
Generation of CTL recognizing an HLA-A*0201-restricted epitope shared by MAGE-A1,-A2,-A3,-A4,-A6,-A10, and-A12 tumor antigens: Implication in a broad-spectrum tumor immunotherapy
复制标题
DOI：
10.4049/jimmunol.169.1.575
复制
发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Kosmatopoulos, K
中科院分区：
文献类型：
--
作者：
Graff-Dubois, S;Faure, O;Kosmatopoulos, K
MAGE-A1、-A2、-A3、-A4、-A6、-A10和-A12在各种组织学类型的原发性和转移性肿瘤中表达，是肿瘤ag特异性CTL的靶点。个体MAGE-A的表达因肿瘤类型而异，但总体而言，绝大多数肿瘤至少表达一种MAGE-A抗原。因此，靶向所有MAGE-A抗原共有的抗原表位将在针对广泛癌症的免疫治疗中引起兴趣。在本研究中，我们描述了一种异位MAGE-A肽（p248V9），它在HLA-A*0201转基因HHD小鼠体内和健康供体体外诱导CTL。这些CTL能够识别来自MAGE-A2、-A3、-A4、-A6、-A10和-A12 （p248G9）和MAGE-A1 （p248D9）的两种低HLA-A*0201亲和肽，它们的c端位置不同。有趣的是，p248v9特异性CTL以HLA-A*0201限制的方式对内源性MAGE-A1、-A2、-A3、-A4、-A6、-A10和-A12产生应答，并识别各种组织学来源的人HLA-A*0201(+)MAGE-A（+）肿瘤细胞。因此，这种异肽可能被认为是一种广谱肿瘤疫苗的有力候选物。
MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 are expressed in a significant proportion of primary and metastatic tumors of various histological types and are targets of tumor Ag-specific CTL. Individual MAGE-A expression varies from one tumor type to the other but, overall, the large majority of tumors expresses at least one MAGE-A Ag. Therefore, targeting epitopes shared by all MAGE-A Ags would be of interest in immunotherapy against a broad spectrum of cancers. In the present study, we describe a heteroclitic MAGE-A peptide (p248V9) that induces CTL in vivo in HLA-A*0201 transgenic HHD mice and in vitro in healthy donors. These CTL are able to recognize two low HLA-A*0201 affinity peptides differing at their C-terminal position and derived from MAGE-A2, -A3, -A4, -A6, -A10, and -A12 (p248G9) and MAGE-A1 (p248D9). Interestingly, p248V9-specific CTL respond to endogenous MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 in an HLA-A*0201-restricted manner and recognize human HLA-A*0201(+)MAGE-A(+) tumor cells of various histological origin. Therefore, this heteroclitic peptide may be considered as a potent candidate for a broad-spectrum tumor vaccination.