Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas.
Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas.
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DOI：
10.4049/jimmunol.163.2.1037
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发表时间：
1999-07
影响因子：
4.4
通讯作者：
Rongcun Yang;Flavio Salazar-Onfray;J. Charo;Karl-Johan Malmberg;Kristina Evrin;H. Maes;Koji Kono;Koji Kono;C. Hising;M. Petersson;Olle Larsson;Li Lan;Ettore Appella;Alessandro Sette;E. Celis;Rolf Kiessling
中科院分区：
文献类型：
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作者：
Rongcun Yang;Flavio Salazar-Onfray;J. Charo;Karl-Johan Malmberg;Kristina Evrin;H. Maes;Koji Kono;Koji Kono;C. Hising;M. Petersson;Olle Larsson;Li Lan;Ettore Appella;Alessandro Sette;E. Celis;Rolf Kiessling
22个新的HLA-A2.1-结合肽来源于原癌基因HER 2/neu的鉴定和分析其能力，以引发肽和肿瘤特异性CTL反应。我们使用来自卵巢癌患者腹水的肽脉冲的自体DC来诱导CTL。在22个测试的新的HER 2/neu衍生的表位中，其可以以高结合率结合HLA-A2。（IC 50 < 50 nM）或中间体（50 nM <IC 50 < 500 nM）亲和力，我们报告了CTL对至少四种新表位的识别，包括HER 2（9435）、HER 2（9665）、HER 2（9689）和HER 2（10952），并证实了已知的HER 2（9369）表位。这些表位能够引发特异性杀伤肽致敏靶细胞的CTL，最重要的是，杀伤HER 2/neu转染的细胞系和自体肿瘤细胞。我们还证实了HER 2/neu在几种黑色素瘤细胞系中过表达，作为一项新发现，报告了其中一些细胞系对HER 2（9369）、HER 2（9435）和HER 2（9689）表位诱导的CTL敏感。最后，从肿瘤特异性CTL系中分离出对HER 2（9369）、HER 2（9435）和HER 2（9689）表位具有特异性的CTL克隆，进一步证明了这些表位的免疫优势。这些发现拓宽了基于HER 2/neu的免疫疗法的潜在应用。
Twenty-two new HLA-A2.1-binding peptides derived from the protooncogene HER2/neu were identified and analyzed for their capacity to elicit peptide and tumor-specific CTL responses. We used peptide-pulsed autologous DC from the ascites of patients with ovarian carcinomas to induce CTL. Of the 22 tested new HER2/neu-derived epitopes that could bind HLA-A2 with high (IC50 < 50 nM) or intermediate (50 nM < IC50 < 500 nM) affinity, we report the recognition by CTL of at least four novel epitopes, including HER2(9435), HER2(9665), HER2(9689), and HER2(10952), and confirm that of the known HER2 (9369) epitope. These epitopes were able to elicit CTL that specifically killed peptide-sensitized target cells and, most importantly, a HER2/neu-transfected cell line and the autologous tumor cells. We also confirm that HER2/neu is overexpressed in several melanoma lines, and as a new finding, report that some of these lines are sensitive to CTL induced by the HER2 (9369), HER2(9435), and HER2(9689) epitopes. Finally, CTL clones specific for HER2 (9369), HER2(9435), and HER2(9689) epitopes were isolated from tumor-specific CTL lines, further demonstrating the immunodominance of these epitopes. These findings broaden the potential application of HER2/neu-based immunotherapy.