Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.

Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.
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胎盘衍生的 gp96 作为多价预防性癌症疫苗

DOI:
10.1038/srep01947
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Meng, Songdong
Meng, Songdong
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao, Bao;Wang, Yanzhong;Wu, Bo;Liu, Shan;Wu, Erjie;Fan, HongXia;Gui, MingMing;Chen, Lizhao;Li, Changfei;Ju, Ying;Zhang, Wei;Meng, Songdong

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设计预防性癌症疫苗的主要挑战是确定免疫原性和安全的癌症抗原。鉴于癌症和胚胎组织之间抗原表达模式的惊人相似性,我们定义了使用胎盘来源的热休克蛋白gp 96的原型策略,其诱导预防性抗肿瘤T细胞应答。用胎盘gp 96免疫小鼠提供了部分保护和长期(至少3个月)抗肿瘤免疫以对抗可移植的黑素瘤或乳腺肿瘤的生长,在大鼠中引发了对抗7,12-二甲基苯并(a)-蒽(DMBA)诱导的乳腺肿瘤的总体保护,并且显著减少了HER 2转基因小鼠中的自体乳腺肿瘤的发生和生长。胎盘gp 96通过结合肿瘤相关抗原激活HER 2和MUC 1特异性T细胞应答。我们的研究结果揭示了胎盘gp 96的新的免疫原性及其作为多价癌症疫苗的潜在用途。
A major challenge for designing prophylactic cancer vaccines is to define immunogenic and safe cancer antigens. Given the striking similarity of antigen expression patterns between cancer and embryonic tissues, we defined a prototype strategy of using placenta-derived heat shock protein gp96, which induces prophylactic anti-tumor T cell responses. Immunization with placental gp96 provided partial protection and long-term (at least 3 months) anti-tumor immunity against growth of transplantable melanoma or breast tumors in mice, elicited total protection against 7, 12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumors in rats and significantly reduced the occurrence and growth of autochthonous breast tumors in HER2 transgenic mice. Placental gp96 activated HER2- and MUC1-specific T cell responses through binding to tumor-associated antigens. Our results reveal the novel immunogenicity of placental gp96 and its potential use as a multivalent cancer vaccine.
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