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多重耐药性重组的CAR-T细胞与异基因相免疫疗法的结合

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发表于 2015-8-20 22:47:33 | 显示全部楼层 |阅读模式
A Multidrug-resistantEngineered CAR T Cell for Allogeneic Combination Immunotherapy
多重耐药性重组的CAR-T细胞与异基因相免疫疗法的结合
The adoptive transfer of chimeric antigen receptor(CAR) T cell represents a highly promising strategy to fight against multiplecancers. The clinical outcome of such therapies is intimately linked to theability of effector cells to engraft, proliferate, and specifically kill tumorcells within patients. When allogeneic CAR T-cell infusion is considered, hostversus graft and graft versus host reactions must be avoided to preventrejection of adoptively transferred cells, host tissue damages and to elicitsignificant antitumoral outcome. This work proposes to address these threerequirements through the development of multidrug-resistant T cell receptorαβ-deficient CAR T cells. We demonstrate that these engineered   T cells displayed efficient antitumoractivity and proliferated in the presence of purine and pyrimidine nucleosideanalogues, currently used in clinic as preconditioning lymphodepletingregimens. The absence of TCRαβ at their cell surface along with their purinenucleotide analogues-resistance properties could prevent their alloreactivityand enable them to resist to lymphodepleting regimens that may be required toavoid their ablation via HvG reaction. By providing a basic framework todevelop a universal T cell compatible with allogeneic adoptive transfer, thiswork is laying the foundation stone of the large-scale utilization of CART-cell immunotherapies.
爱康得生物医学编译:
嵌合抗原受体T细胞的过继免疫治疗在多种肿瘤的治疗中具有广阔的前景。这种疗法的临床结果和效应细胞在患者体内并在体的增殖能力,以及特异性杀死肿瘤细胞的能力密切相关。当同种异体CAR-T细胞输注体内时,必须避免宿主抗移植物和移植物抗宿主反应,以防止机体排斥过继移植的细胞或移植的细胞对宿主组织损害,但同时也要保证对宿主肿瘤的杀伤作用。这项工作中作者提出研发多重耐药T细胞受体αβ缺陷CAR-T细胞的三个要求,证明了这些重组的细胞显示出了有效的抗肿瘤活性以及在嘌呤,嘧啶核苷类似物作用下的增殖能力:这些类似物目前在临床上被广泛用作在预处理淋巴细胞方案中。由于这些新型CAR-T细胞表面没有TCRαβ,因此它们的具备抵抗嘌呤核苷酸类似物抗性性能,可以防止由这些药物引起的淋巴细胞的消融。作者希望通过这一个基本的框架来开发可在同种异体过继免疫治疗中使用的通用T细胞,这项工作是铺设大规模利用CAR-T细胞免疫治疗的基石。
详见:
http://www.icartab.com.cn/details.html?article_id=67

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