Application of Heat-shock protein with antigenic peptide for cancer vaccine

热激蛋白抗原肽在癌症疫苗中的应用

• 批准号: 14571146
• 负责人: NAGATA Yasuhiro
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571146/
• 关键词: Heat-shock protein; Cancer Vaccine; NY-ESO-I; Dendritic Cell; hsc70

Heat shock proteins(HSPs) 70 are a family of highly conserved molecules with ATPase activity and relative molecular masses around 70,000 kDa. Hsp proteins chaperone antigenic peptides into antigen-presenting cells, potentially allowing peptides to enter the MHC class I pathway for loading onto MHC class I molecules, where they can be presented to cytotoxic CD8+ T cells. In turn, this. provides a strategy for immunization against cancer by using hsp and bound peptides that are isolated from tumors. Immunization with heat shock cognate protein 70 (hsc70) bound to synthetic peptides by in vitro reconstitution has been shown to induce peptide-specific CTL in mice. Here, we succeed genetically to fuse hsc70 and a. CTL epitope derived from NY ESO-I, one of the cancer-testis antigens. We also have shown dendritic cell can present, the epitope onto their MHC class I after feeding the fusion protein. Hsc70 with NY ESO-1 peptide can be processed through cytosolic pathway and presented by DCs to CD8^+ T cell clones. These findings help devising and validating vaccine strategies with Hsc-NY ESO-l epitope fusion protein.

热休克蛋白（HSPs） 70是一个高度保守的分子家族，具有atp酶活性，相对分子质量约为70000 kDa。热休克蛋白伴随抗原肽进入抗原呈递细胞，潜在地允许肽进入MHC I类途径，装载到MHC I类分子上，在那里它们可以被呈递到细胞毒性CD8+ T细胞。反过来，这。提供了一种利用从肿瘤中分离的热休克蛋白和结合肽对癌症进行免疫的策略。热休克同源蛋白70 （hsc70）通过体外重组与合成肽结合免疫，已被证明可在小鼠体内诱导肽特异性CTL。在这里，我们成功地通过基因融合了hsc70和来自NY ESO-I的a. CTL表位，这是一种癌症睾丸抗原。我们还发现树突状细胞在喂食融合蛋白后可以将表位呈现到它们的MHC I类上。含有NY ESO-1肽的Hsc70可通过胞质途径加工，并通过dc呈递给CD8^+ T细胞克隆。这些发现有助于设计和验证Hsc-NY eso - 1表位融合蛋白的疫苗策略。

项目成果

Yasuhiro Nagata et al.: "Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendreitc cell populations"Proceedings of the National Academy of Sciences. Vol.99 No.16. 10629-10634 (2002)

Yasuhiro Nagata 等人：“不同的人树突状细胞群对可溶性外源肿瘤抗原 NY-ESO-1 的差异呈递”，《美国国家科学院院刊》。

Tominaga N, et al.: "Development of Th1 and Th2 immune responses in mice lacking interferon regulatory factor-4."Int.Immuuol.. 15. 1-10 (2003)

Tominaga N 等人：“缺乏干扰素调节因子 4 的小鼠中 Th1 和 Th2 免疫反应的发展。”Int.Immuuol.. 15. 1-10 (2003)

Yamano T, Murata S, 他: "Two distinct pathways mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing."J Exp Med.. 196・2. 185-196 (2002)

Yamano T、Murata S 等人：“主要组织相容性复合物 I 类抗原加工中由 PA28 和 hsp90 介导的两种不同途径。”J Exp Med. 196・2 (2002)。

Udono H, et al.: "Hsp-antigen fusion and their use for immunization."Methods.. June 32(1). 21-24 (2004)

Udono H 等人：“Hsp-抗原融合及其在免疫中的用途。”方法.. 6 月 32 日（1）。

Yamano T, et al.: "Two distinct pathway mediated by PA28 and hsp90 in major histocompatibility complex class I antigen processing."J.ExMed.. 196. 185-196 (2002)

Yamano T 等人：“在主要组织相容性复合物 I 类抗原加工中由 PA28 和 hsp90 介导的两种不同途径。”J.ExMed.. 196. 185-196 (2002)