Cytotoxic T lymphocyte epitopes from human heparanase can elicit a potent anti-tumor immune response in mice
Cytotoxic T lymphocyte epitopes from human heparanase can elicit a potent anti-tumor immune response in mice
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人乙酰肝素酶的细胞毒性 T 淋巴细胞表位可在小鼠体内引发有效的抗肿瘤免疫反应
DOI：
10.1007/s00262-010-0829-x
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
汤旭东
中科院分区：
文献类型：
--
作者：
汤旭东
乙酰肝素酶在几乎所有的晚期肿瘤中都有表达，因此它可能成为肿瘤治疗的潜在靶点。我们前期的研究表明，乙酰肝素酶可作为一种潜在的肿瘤相关抗原（TAA）用于晚期肿瘤的免疫治疗。进一步的研究表明，HLA-A*0201限制性细胞毒性T淋巴细胞（CTL）表位Hpa 525（PAFSYSFFV）、Hpa 277（KMLKSFLKA）和Hpa 405（WLSLLFKKL）在体外可诱导有效的抗肿瘤免疫应答。本研究旨在研究上述肽是否能诱导小鼠产生免疫应答。我们的研究结果表明，来自乙酰肝素酶肽免疫小鼠的效应物可以有效地裂解乙酰肝素酶阳性且HLA-A*0201匹配的各种肿瘤细胞。我们还发现，这些肽特异性CTL不裂解具有低乙酰肝素酶活性的自体淋巴细胞。进一步的研究表明，与阴性肽相比，Hpa 525、Hpa 277和Hpa 405肽增加了产生IFN-γ的T细胞的频率。这些结果表明Hpa 525、Hpa 277和Hpa 405肽是新型HLA-A*0201限制性CTL表位，能够在小鼠中诱导乙酰肝素酶特异性CTL。由于乙酰肝素酶在大多数晚期恶性肿瘤中表达，因此基于Hpa 525、Hpa 277和Hpa 405肽的疫苗可能对晚期肿瘤患者的免疫治疗有用。
Heparanase is expressed in almost all advanced tumors, and therefore it may serve as a potential target for tumor therapy. Our previous study has shown that heparanase can serve as a potential universal tumor-associated antigen (TAA) for the immunotherapy of advanced tumors. Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro. The present study was designed to investigate whether the above peptides could induce immune responses in mice. Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched. We also found that these peptide-specific CTLs did not lyse autologous lymphocytes that had low heparanase activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-γ-producing T cells as compared to a negative peptide. These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice. Because heparanase is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide-based vaccines may be useful for the immunotherapy of patients with advanced tumors.
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影响因子：
4.6
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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