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首页> 外文期刊>Molecular therapy: the journal of the American Society of Gene Therapy >Induction of tumor-specific immune response by gene transfer of Hsp70-cell-penetrating peptide fusion protein to tumors in mice.
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Induction of tumor-specific immune response by gene transfer of Hsp70-cell-penetrating peptide fusion protein to tumors in mice.

机译：Hsp70细胞穿透性肽融合蛋白向小鼠肿瘤的基因转移诱导肿瘤特异性免疫反应。

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To induce a tumor-specific immune response by delivering tumor-associated antigens in tumor cells to antigen-presenting cells (APCs), we designed a fusion protein which consists of heat-shock protein 70 (Hsp70) and the C-terminal 34 amino acids of herpes simplex virus VP22 protein (VP22(268-301)), the former having a peptide binding domain and an ability to be recognized by APCs, and the latter able to achieve cell penetration. Hsp70-VP22(268-301), the fusion protein, was efficiently taken up by mouse dendritic cell (DC) line DC2.4. Major histocompatibility complex (MHC) class I-restricted presentation of an epitope peptide of ovalbumin (OVA) was examined in DC2.4, and Hsp70-VP22(268-301) significantly increased the presentation of the peptide compared with Hsp70. Electroporation-assisted injection of naked plasmid vector expressing Hsp70-VP22(268-301) (pHsp70-VP22(268-301)) into subcutaneous tumors of EG7-OVA, a mouse lymphoma-expressing OVA, significantly increased the survival of mice compared with the same treatment with pHSp70, a plasmid expressing Hsp70. Splenocytes from the pHsp70-VP22(268-301)-treated mice exhibited cytolytic activity against both EG7-OVA and the parent EL4, but not against mouse melanoma B16-F10, suggesting that not only OVA-derived antigens but those common to EG7-OVA and EL4 are delivered to APCs. These results provide a new therapeutic method to induce tumor-specific antitumor immunity without identifying nor isolating tumor-associated antigens.
机译：为了通过将肿瘤细胞中的肿瘤相关抗原传递给抗原呈递细胞（APC）来诱导肿瘤特异性免疫反应，我们设计了一种融合蛋白，该融合蛋白由热休克蛋白70（Hsp70）和C端34个氨基酸组成单纯疱疹病毒VP22蛋白（VP22（268-301）），前者具有肽结合结构域并具有被APC识别的能力，后者能够实现细胞渗透。 Hsp70-VP22（268-301），融合蛋白，被小鼠树突状细胞（DC）系DC2.4有效吸收。在DC2.4中检查了主要组织相容性复合物（MHC）I类限制的卵清蛋白（OVA）表位肽的呈递，与Hsp70相比，Hsp70-VP22（268-301）显着增加了该肽的呈递。电穿孔辅助将表达Hsp70-VP22（268-301）（pHsp70-VP22（268-301））的裸质粒载体注射到表达小鼠淋巴瘤的卵母细胞EG7-OVA的皮下肿瘤中，与之相比，小鼠的存活率显着提高用pHSp70（表达Hsp70的质粒）进行相同的处理。来自经pHsp70-VP22（268-301）处理的小鼠的脾细胞对EG7-OVA和亲本EL4均表现出细胞溶解活性，但对小鼠黑素瘤B16-F10则没有，提示这不仅是OVA衍生的抗原，而且是EG7-共同的抗原。 OVA和EL4已交付给APC。这些结果提供了诱导肿瘤特异性抗肿瘤免疫而不识别或分离肿瘤相关抗原的新治疗方法。

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