Potent antitumor effect elicited by superantiaen-linked tumor cells transduced with heat shock protein 70 gene
Potent antitumor effect elicited by superantiaen-linked tumor cells transduced with heat shock protein 70 gene
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DOI：
10.1111/j.1349-7006.2004.tb03198.x
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发表时间：
2004-02-01
期刊：
影响因子：
5.7
通讯作者：
Cao, XT
中科院分区：
文献类型：
--
作者：
Huang, CX;Yu, H;Cao, XT
热休克蛋白(HSP)通过一种独特的机制诱导抗肿瘤特异性免疫，但单独使用HSP不能产生令人满意的抗肿瘤效果。我们认为，超抗原(SAG)的强大免疫激活作用可能有助于HSP诱导较强的肿瘤抗原特异性免疫。我们最初制备了与SAG连接的B16黑色素瘤细胞。SEA-通过与跨膜序列(TM)的融合蛋白，证明了这样锚定在肿瘤细胞表面的SEA可以诱导强大的抗肿瘤免疫。然后，我们制备了转导可诱导热休克蛋白70(HSP70)基因的细胞，并在细胞表面携带SEA-TM融合蛋白，并将其用作双重修饰疫苗。在本研究中，无论是在治疗环境中，还是在预免疫模型中，SEA锚定疫苗和HSP70基因修饰疫苗都能显著抑制C57BL/6小鼠的肿瘤生长，延长其存活时间，促进淋巴细胞增殖，并提高墨汁和CTL活性(P
Heat shock proteins (HSP) induce antitumor-specific immunity via a unique mechanism, but HSP alone fails to produce a satisfactory antitumor efficacy. We considered that the potent immune-activation of superantigen (SAg) might assist HSP to elicit a strong tumor-antigen-specific immunity. We initially prepared B16 melanoma cells linked to SAg. SEA-via a fusion protein with a transmembrane sequence (TM), and demonstrated that SEA thus anchored on the tumor cell surface could elicit strong antitumor immunity. We then prepared cells transduced with an inducible heat shock protein 70 (HSP70) gene, and bearing SEA-TM fusion protein on the cell surface, and used these cells as a dual-modified vaccine. In this study, either in a therapeutic setting or in a pre-immune model, the SEA-anchored vaccine or the HSP70 gene-modified vaccine induced marked tumor suppression, prolonged survival, augmented lymphocyte proliferation and higher INK and CTL activity in C57BL/6 mice compared with their controls (P