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热休克蛋白 65 与 β-hCG 串联重复融合蛋白作为一种有效的肿瘤疫苗抑制肝癌。

The fusion protein of HSP65 with tandem repeats of beta-hCG acting as a potent tumor vaccine in suppressing hepatocarcinoma.

机构信息

Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, PR China.

出版信息

Int Immunopharmacol. 2010 Feb;10(2):230-8. doi: 10.1016/j.intimp.2009.11.006. Epub 2009 Nov 11.

Abstract

It has been demonstrated that the beta-subunit of human chorionic gonadotropin (beta-hCG) is ectopically expressed on a variety of human cancers of different histological types and has been used as an antigenic target in anti-cancer vaccines. We engineered a fusion protein by fusing 10 tandemly repeated copies of the 10-residue sequence of beta-hCG (109-118) (in CTP37) combined with beta-hCG C-terminal 37 peptides to mycobacterial heat-shock protein 65 and immunized mice via subcutaneous injection. Humoral immune and cellular immune responses were effectively elicited. High titer of anti-beta-hCG antibody was detected in immunized mice sera by ELISA and verified by Western blot analyses. The fusion protein of HSP65-X10-beta-hCGCTP37 effectively inhibited the growth of tumor both protective and therapeutic anti-tumor immunity in hepatocellular carcinoma tumor models in mice. Meanwhile, it also attenuated tumor-induced angiogenesis in intradermal tumor model in mice. Taken together, these results demonstrate that immune responses are effectively induced by a novel fusion protein vaccine targeting beta-hCG, suppressing the growth of hepatocellular carcinoma in mice. The beta-hCG-targeted vaccine holds promise for the treatment of a number of cancers and merits further study.

摘要

已经证实,人绒毛膜促性腺激素(β-hCG)的β亚单位在不同组织类型的多种人类癌症中异位表达,并已被用作抗癌疫苗中的抗原靶标。我们通过将 10 个串联重复的β-hCG(109-118)(CTP37 中)的 10 个残基序列与β-hCG C 端 37 个肽融合,构建了一种融合蛋白,并通过皮下注射将其免疫小鼠。有效地引发了体液免疫和细胞免疫反应。通过 ELISA 检测到免疫小鼠血清中抗-β-hCG 抗体的高滴度,并用 Western blot 分析进行了验证。HSP65-X10-β-hCGCTP37 融合蛋白在小鼠肝癌肿瘤模型中有效抑制肿瘤生长,具有保护和治疗性抗肿瘤免疫作用。同时,它还减弱了小鼠皮内肿瘤模型中的肿瘤诱导血管生成。总之,这些结果表明,针对β-hCG 的新型融合蛋白疫苗可有效诱导免疫反应,抑制小鼠肝癌的生长。β-hCG 靶向疫苗有望治疗多种癌症,值得进一步研究。

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