Huang Changxin, Yu Hai, Wang Qingqing, Yang Guangen, Ma Wenxue, Xia Dajing, Chen Xiaohong, Yi Pingyong, Shen Fengping, Zheng Haiya, Cao Xeutao
The Third People's Hospital Hangzhou, PR China.
Immunol Lett. 2005 Oct 15;101(1):71-80. doi: 10.1016/j.imlet.2005.04.009.
Heat shock proteins (HSP) are attractive for their initiation of anticancer specific immunity via a distinct mechanism. To facilitate the induction process, we targeted HSP onto vaccine cell surface genetically. Then, SEA (a typical superantigen) was anchored on the cells by its fusion protein with transmembrane sequence, in order to produce immune-activated microsurrounding for further improvement of specific immunity. Thereby, the dual-modified vaccine, the surface-targeting-HSP70 and SEA-anchored vaccine, was developed successfully. Both in a therapeutic setting and in a pre-immune model, the mice vaccinated with the dual-modified vaccine displayed significant lymphocyte proliferation, higher NK and CTL activity, marked tumor suppression and prolonged survival when compared with those vaccinated with the vaccine modified alone with surface-targeting HSP70 or the SEA-anchored vaccine. Of all the vaccines, the dual-modified vaccine generated the best therapeutic efficacy on melanoma-bearing mice, the strongest protection against melanoma challenge. These results suggested that the dual-modified vaccine could induce more potent anticancer specific immunity while non-specific immunity was augmented.
热休克蛋白（HSP）因其通过独特机制引发抗癌特异性免疫而备受关注。为促进诱导过程，我们通过基因手段将HSP靶向到疫苗细胞表面。然后，SEA（一种典型的超抗原）通过其与跨膜序列的融合蛋白锚定在细胞上，以产生免疫激活的微环境，进一步增强特异性免疫。由此，成功研发出双修饰疫苗，即表面靶向HSP70和SEA锚定疫苗。无论是在治疗环境还是在免疫前模型中，与接种仅经表面靶向HSP70修饰的疫苗或SEA锚定疫苗的小鼠相比，接种双修饰疫苗的小鼠表现出显著的淋巴细胞增殖、更高的NK和CTL活性、明显的肿瘤抑制作用以及更长的生存期。在所有疫苗中，双修饰疫苗对荷黑素瘤小鼠产生的治疗效果最佳，对黑素瘤攻击的保护作用最强。这些结果表明，双修饰疫苗在增强非特异性免疫的同时，能够诱导更强大的抗癌特异性免疫。
