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nature好文分享嵌合抗原受体修饰的T细胞做为溶瘤病毒的载体

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发表于 2015-11-3 22:29:25 | 显示全部楼层 |阅读模式
Chimeric antigen receptor–engineered T cells as oncolytic virus carriers
嵌合抗原受体修饰的T细胞做为溶瘤病毒的载体


The use of engineered T cells in adoptive transfer therapies has shown significant promise in treating hematological cancers.However, successes treating solid tumors are much less prevalent. Oncolytic viruses (OVs) have the capacity to induce specific lysis of tumor cells and indirectly impact tumor growth via vascular shutdown. These viruses bear natural abilities to associate with lymphocytes upon systemic administration, but therapeutic doses must be very high in order to evade antibodies and other components of the immune system. As T cells readily circulate through the body, using these cells to deliver OVs directly to tumors may provide an ideal combination. Our studies demonstrate that loading chimeric antigen receptor–engineered T cells with low doses of virus does not impact receptor expression or function in either murine or human T cells. Engineered T cells can deposit virus onto a variety of tumor targets, which can enhance the tumoricidal activity of the combination treatment. This concept appears to be broadly applicable, as we observed similar results using murine or human T cells, loaded with either RNA or dna viruses. Overall,loading of engineered T cells with OVs represents a novel combination therapy that may increase the efficacy of both treatments.

改造的T细胞过继免疫治疗在治疗血液肿瘤中展现了卓越的前景。然而,成功治疗实体肿瘤还是并不普遍。 溶瘤病毒(OVS)有能力诱导肿瘤特异性溶解,并且能够通过关闭血管影响肿瘤生长。这些病毒的耐受能力与淋巴系统相关,治疗的剂量必须非常高,来逃避抗体和免疫系统的其他部分。因为T细胞很容易通过体循环,使用这些细胞来直接传递溶瘤病毒(OVS)到癌细胞可能会提供一个理想的组合。我们的研究表明,不管在小鼠还是人的嵌合抗原受体修饰的T细胞在低剂量的病毒负载下没有影响受体的表达和功能。改造的T细胞能够将病毒沉积到肿瘤的多个靶点上,从而能够联合增强肿瘤杀伤活性。这个概念似乎是普遍适用的,因为我们观察到相同的结果,当使用不管是RNA病毒或者是DNA病毒负载在小鼠或者人的T细胞上。总的来说,加载OVS的改造T细胞代表了一种新的联合治疗,可以提高治疗的疗效。





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