Immunization with a HER-2/neu helper peptide generates HER-2/neu CD8 T-cell immunity in cancer patients
Immunization with a HER-2/neu helper peptide generates HER-2/neu CD8 T-cell immunity in cancer patients
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DOI：
10.1172/jci11752
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发表时间：
2001-02-01
影响因子：
15.9
通讯作者：
Disis, ML
中科院分区：
文献类型：
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作者：
Knutson, KL;Schiffman, K;Disis, ML
在产生和维持有效的抗肿瘤CD8 T细胞介导的免疫力期间，需要CD4 T细胞的帮助。本研究的目的是确定HER-2/neu特异性CD8 T细胞免疫是否可以使用HER-2/neu衍生的MHC II类"辅助"肽（包含HLA-A2结合基序）引发。19名HER-2/neu过表达癌症的HLA-A2患者接受了由推定的HER-2/neu辅助肽p369 - 384、p688 - 703和p971 - 984组成的疫苗制剂。这些序列中包含HLA-A2结合基序p369 - 377、p689 - 697和p971 - 979。接种疫苗后，大多数患者HLA-A2肽的平均肽特异性T细胞前体频率增加。此外，肽特异性T细胞能够溶解肿瘤。在选定的患者中，应答持续时间较长，在末次接种疫苗后1年以上仍可检测到。这些结果表明，含有包含的MHC I类表位的HER-2/neu MHC II类表位能够诱导持久的HER-2特异性IFN-γ产生性CD8 T细胞。
CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell-mediated immunity. The goal of this study was to determine whether HER-2/neu-specific CD8 T-cell immunity could be elicited using HER-2/neu-derived MHC class II "helper" peptides, which contain encompassed HLA-A2-binding motifs. Nineteen HLA-A2 patients with HER-2/neu-overexpressing cancers received a vaccine preparation consisting of putative HER-2/neu helper peptides p369-384, p688-703, and p971-984. Contained within these sequences are the HLA-A2-binding motifs p369-377, p689-697, and p971-979. After vaccination, the mean peptide-specific T-cell pre cursor frequency to the HLA-A2 peptides increased in the majority of patients. In addition, the peptide-specific T cells were able to lyse tumors. The responses were long lived and detectable for more than 1 year after the final vaccination in select patients. These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2-specific IFN-gamma -producing CD8 T cells.