Huang Changxin, Yu Hai, Wang Qingqing, Ma Wenxue, Xia Dajing, Yi Pingyong, Zhang Lihuang, Cao Xuetao
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
Cancer Sci. 2004 Feb;95(2):160-7. doi: 10.1111/j.1349-7006.2004.tb03198.x.
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 NK and CTL activity in C57BL/6 mice compared with their controls (P < 0.01), though they were less effective than the dual-modified vaccine. Among these vaccines, the dual-modified vaccine showed the best therapeutic efficacy in B16 melanoma-bearing mice and gave the greatest protection against wild-type B16 melanoma challenge. The results indicated that the dual-modified vaccine could induce a potent tumor-antigen-specific immune response in addition to an increase of non-specific immunity. This study offers a novel approach to bridging specific and non-specific immunity for cancer therapy.
热休克蛋白（HSP）通过一种独特机制诱导抗肿瘤特异性免疫，但单纯的HSP未能产生令人满意的抗肿瘤疗效。我们认为超抗原（SAg）的强大免疫激活作用可能有助于HSP引发强烈的肿瘤抗原特异性免疫。我们最初通过一种具有跨膜序列（TM）的融合蛋白制备了与SAg SEA相连的B16黑色素瘤细胞，并证明如此锚定在肿瘤细胞表面的SEA能够引发强烈的抗肿瘤免疫。然后我们制备了转导有诱导型热休克蛋白70（HSP70）基因且细胞表面带有SEA - TM融合蛋白的细胞，并将这些细胞用作双修饰疫苗。在本研究中，无论是在治疗环境还是在免疫前模型中，与对照组相比，SEA锚定疫苗或HSP70基因修饰疫苗在C57BL / 6小鼠中均诱导了显著的肿瘤抑制、延长了生存期、增强了淋巴细胞增殖以及提高了NK和CTL活性（P < 0.01），尽管它们的效果不如双修饰疫苗。在这些疫苗中，双修饰疫苗在携带B16黑色素瘤的小鼠中显示出最佳的治疗效果，并对野生型B16黑色素瘤攻击提供了最大程度的保护。结果表明，双修饰疫苗除了增强非特异性免疫外，还能诱导强大的肿瘤抗原特异性免疫反应。本研究为癌症治疗中连接特异性和非特异性免疫提供了一种新方法。
