新浪登录
腾讯登录Hum Gene Ther：新方法阻止身体对治疗性蛋白产生排斥反应
| 导读 | 身体对替换蛋白(replacement protein)产生排斥作用的自然反应代表着成功利用基因疗法治疗一系列危及生命的疾病时所面临的一个主要障碍。然而，根据一篇发表在<em>Human Gene Therapy</em>期刊上的论文，研究人员开发出一种新方法：利用身体自己的免疫细胞诱导身体对特异性蛋白产生耐受性，并且证实该方法能够抑制这种排斥反应。
美国宾夕法尼亚大... |
身体对替换蛋白(replacement protein)产生排斥作用的自然反应代表着成功利用基因疗法治疗一系列危及生命的疾病时所面临的一个主要障碍。然而，根据一篇发表在<em>Human Gene Therapy</em>期刊上的论文，研究人员开发出一种新方法：利用身体自己的免疫细胞诱导身体对特异性蛋白产生耐受性，并且证实该方法能够抑制这种排斥反应。
美国宾夕法尼亚大学佩雷尔曼医学院教授James M. Wilson说，“蛋白和基因治疗方法的一个主要限制就是与之相关联的免疫反应，这种反应能够产生毒性和降低疗效。巧妙地利用免疫调节物可能阻止免疫反应发生。”
<!--more-->
在被称作细胞因子的免疫刺激化合物存在下，让一类被称作树突细胞的免疫细胞接触一种特异性的治疗性蛋白能够导致免疫耐受性的树突细胞产生。当耐受性树突细胞被导入小鼠体内时，接着再给小鼠进行经设计能够运送治疗性蛋白的基因疗法治疗，这样这些细胞就允许小鼠对治疗性蛋白产生耐受性，而不是排斥它。
当前诱导对通过基因疗法而产生的替换蛋白产生部分或完全耐受性的方法是比较昂贵，而且失败率高达40%。在这项研究中，研究人员开发出的这种方法在这方面具有优势，能够促进基因疗法的长期成功。
本文编译自<a href="http://www.sciencenewsline.com/articles/2012080723430013.html" target="_blank">Method to Prevent Rejection of Disease-fighting Proteins Described in Human Gene Therapy Journal </a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080822533580.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1089/hum.2011.225" target="_blank">doi: 10.1089/hum.2011.225</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice</strong><br/>
Gautam Sule, Masataka Suzuki, Kilian Guse, Racel Cela, John R. Rodgers, and Brendan Lee
A major obstacle in the genetic therapy of inherited metabolic disease is host immune responses to the therapeutic protein. This is best exemplified by inhibitor formation in the protein therapy for hemophilia A. An approach to overcoming this is induction of immunological tolerance to the therapeutic protein. Tolerogenic dendritic cells (DCtols) have been reported to induce tolerance. In addition, cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β1 are known to induce tolerance. To model protein therapy, we used ovalbumin (OVA) as antigen in BALB/c mice and their transgenic derivative, DO11.10 mice. In this study we show that adoptive transfer of antigen-pulsed dendritic cells (DCs) treated with a combination of IL-10 and TGF-β1 can suppress the antibody response in mice. Adoptive transfer of cytokine-conditioned DCs in preimmunized mice results in reduction of antibody response in the mice. Furthermore, the effect is antigen specific, as the recipient mice were able to mount a potent antibody response to the control antigen. Last, we show that TGF-β1 and IL-10-conditioned DCs are able to inhibit anti-FVIII antibody responses in FVIII knockout (KO) mice. Analysis of the contribution of IL-10 and TGF-β1 to the DCtol phenotype shows that IL-10 treatment of DCs is sufficient for inducing OVA-specific tolerance in BALB/c mice, but we observed a requirement for treatment with both human TGF-β1 and human IL-10 to significantly inhibit anti-FVIII antibody responses in FVIII KO mice. This paper demonstrates that autologous cell therapy for antigen-targeted immune suppression may be developed to facilitate long-term therapy.
<br/>来源：生物谷
</div>
</div>
</div>
美国宾夕法尼亚大学佩雷尔曼医学院教授James M. Wilson说，“蛋白和基因治疗方法的一个主要限制就是与之相关联的免疫反应，这种反应能够产生毒性和降低疗效。巧妙地利用免疫调节物可能阻止免疫反应发生。”
<!--more-->
在被称作细胞因子的免疫刺激化合物存在下，让一类被称作树突细胞的免疫细胞接触一种特异性的治疗性蛋白能够导致免疫耐受性的树突细胞产生。当耐受性树突细胞被导入小鼠体内时，接着再给小鼠进行经设计能够运送治疗性蛋白的基因疗法治疗，这样这些细胞就允许小鼠对治疗性蛋白产生耐受性，而不是排斥它。
当前诱导对通过基因疗法而产生的替换蛋白产生部分或完全耐受性的方法是比较昂贵，而且失败率高达40%。在这项研究中，研究人员开发出的这种方法在这方面具有优势，能够促进基因疗法的长期成功。
本文编译自<a href="http://www.sciencenewsline.com/articles/2012080723430013.html" target="_blank">Method to Prevent Rejection of Disease-fighting Proteins Described in Human Gene Therapy Journal </a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080822533580.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1089/hum.2011.225" target="_blank">doi: 10.1089/hum.2011.225</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Cytokine-Conditioned Dendritic Cells Induce Humoral Tolerance to Protein Therapy in Mice</strong><br/>
Gautam Sule, Masataka Suzuki, Kilian Guse, Racel Cela, John R. Rodgers, and Brendan Lee
A major obstacle in the genetic therapy of inherited metabolic disease is host immune responses to the therapeutic protein. This is best exemplified by inhibitor formation in the protein therapy for hemophilia A. An approach to overcoming this is induction of immunological tolerance to the therapeutic protein. Tolerogenic dendritic cells (DCtols) have been reported to induce tolerance. In addition, cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β1 are known to induce tolerance. To model protein therapy, we used ovalbumin (OVA) as antigen in BALB/c mice and their transgenic derivative, DO11.10 mice. In this study we show that adoptive transfer of antigen-pulsed dendritic cells (DCs) treated with a combination of IL-10 and TGF-β1 can suppress the antibody response in mice. Adoptive transfer of cytokine-conditioned DCs in preimmunized mice results in reduction of antibody response in the mice. Furthermore, the effect is antigen specific, as the recipient mice were able to mount a potent antibody response to the control antigen. Last, we show that TGF-β1 and IL-10-conditioned DCs are able to inhibit anti-FVIII antibody responses in FVIII knockout (KO) mice. Analysis of the contribution of IL-10 and TGF-β1 to the DCtol phenotype shows that IL-10 treatment of DCs is sufficient for inducing OVA-specific tolerance in BALB/c mice, but we observed a requirement for treatment with both human TGF-β1 and human IL-10 to significantly inhibit anti-FVIII antibody responses in FVIII KO mice. This paper demonstrates that autologous cell therapy for antigen-targeted immune suppression may be developed to facilitate long-term therapy.
<br/>来源：生物谷
</div>
</div>
</div>
还没有人评论，赶快抢个沙发