...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Vaccine >A mutant B7-1/Ig fusion protein that selectively binds to CTLA-4 ameliorates anti-tumor DNA vaccination and counters regulatory T cell activity
【24h】

A mutant B7-1/Ig fusion protein that selectively binds to CTLA-4 ameliorates anti-tumor DNA vaccination and counters regulatory T cell activity

机译：选择性结合CTLA-4的突变B7-1 / Ig融合蛋白可改善抗肿瘤DNA疫苗接种并抵抗调节性T细胞活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have shown that a plasmid encoding a B7-1/Ig fusion protein enhanced DNA vaccination against human carcinoembryonic antigen (CEA) more effectively than the plasmid encoding membrane-bound B7-1. However, it was not known if B7-1/Ig acted only by binding CD28 (amplifying a stimulatory signal) or by blocking CTLA-4 on T cells (removing inhibitory signals). Here, we aimed to determine this using a plasmid encoding mutant B7-1/Ig (B7-1wa/Ig), which binds only to CTLA-4 but not to CD28. Our results showed that both the B7-1/Ig and B7-1wa/Ig plasmids, when co-administered with a CEA plasmid, enhanced tumor rejection and the in vitro anti-CEA response. Therefore, B7-1wa/Ig ameliorates DNA vaccination, presumably by binding to CTLA-4. This could result from a number of non-exclusive mechanisms, such as a reduced threshold for T-cell activation, or blockade of CTLA-4/B7-mediated tolerogenic signals in DCs or T cells. We found that, in vitro, a significant fraction of CD3/CD28-activated T cells (in the absence of DCs) expressed CTLA-4 and B7-1. Primed T cells of CTLA-4(+)B7-1(+/-) phenotype acted as regulatory T cells by inhibiting IFNgamma production by re-stimulated CTLA-4(-)B7-1(-) cells, and this was reversed by antibodies against IL-10 or TGF-beta1. Both B7-1wa/Ig and CTLA-4/Ig, which bind to CTLA-4 and B7-1/B7-2 respectively, enhanced IFNgamma production, but not the proliferation or IL-4 release in mixed T-cell populations containing these two cell types. In contrast, CTLA-4(-)B7-1(-) T cells produced IFNgamma which was not affected by B7-1wa/Ig or CTLA-4/Ig. These results suggest that blocking of CTLA-4/B7-1 binding in T cell/T cell interactions blocks negative regulatory signals. This might be the mechanism, at least in part, of the enhancement of anti-tumor immunity by the B7-1wa/Ig and B7-1/Ig plasmids.
机译：我们已经表明，编码B7-1 / Ig融合蛋白的质粒比编码膜结合B7-1的质粒更有效地增强了针对人癌胚抗原（CEA）的DNA疫苗接种。但是，尚不知道B7-1 / Ig是否仅通过结合CD28（放大刺激信号）或通过阻断T细胞上的CTLA-4（去除抑制信号）起作用。在这里，我们旨在使用编码突变体B7-1 / Ig（B7-1wa / Ig）的质粒确定这一点，该突变体仅与CTLA-4结合而不与CD28结合。我们的结果表明，当与CEA质粒共同施用时，B7-1 / Ig和B7-1wa / Ig质粒均增强了肿瘤排斥反应和体外抗CEA应答。因此，B7-1wa / Ig可以通过结合CTLA-4来改善DNA疫苗接种。这可能是由于多种非排他性机制导致的，例如降低了T细胞活化的阈值，或阻断了DC或T细胞中CTLA-4 / B7介导的致耐受性信号。我们发现，在体外，大部分CD3 / CD28激活的T细胞（在没有DC的情况下）表达CTLA-4和B7-1。引发的CTLA-4（+）B7-1（+/-）表型T细胞通过抑制再刺激的CTLA-4（-）B7-1（-）细胞产生的IFNγ来发挥调节性T细胞的作用，这一点被逆转通过针对IL-10或TGF-beta1的抗体。分别与CTLA-4和B7-1 / B7-2结合的B7-1wa / Ig和CTLA-4 / Ig都增强了IFNγ的产生，但不增强含有这些的混合T细胞群体的增殖或IL-4释放。两种细胞类型。相反，CTLA-4（-）B7-1（-）T细胞产生的IFNγ不受B7-1wa / Ig或CTLA-4 / Ig的影响。这些结果表明，在T细胞/ T细胞相互作用中阻断CTLA-4 / B7-1结合会阻断负调控信号。这可能是至少部分通过B7-1wa / Ig和B7-1 / Ig质粒增强抗肿瘤免疫力的机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号