Gamma-delta T cells are optimal immune cell carrier vehicles for adenovirus vector-based gene therapy

Yuki Hasebe, Michio Naoe
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Abstract

Gene therapy is a promising technique for treating malignant tumors. The efficacy of gene therapy with Ad5 is not high although adenovirus type 5 (Ad5) is a common vector, and this may be linked to the low gene transduction rate of Ad5 vectors. The rate of target transduction by Ad has enhanced with the invention of fiber-modified Ad (Ad5/F35); nevertheless, a carrier system for Ad5/F35-based gene delivery is needed. Therefore, we evaluated the possibility of using γδ T cells, which portray high toxicity against cancer cells, as Ad5/F35 vector transporters. In vitro, γδ T cells were more efficient Ad5/F35 vector transporters than human peripheral blood mononuclear cells and natural killer cells tested. Moreover, they could transport the vector to the tumor site in a subcutaneous prostate cancer model in vivo. We conclude that virus-loaded γδ T-cells may aid systemic cancer virotherapy.
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γ - δ T细胞是腺病毒载体基因治疗的最佳免疫细胞载体
基因治疗是一种很有前途的恶性肿瘤治疗技术。虽然腺病毒5型(Ad5)是一种常见的载体,但Ad5基因治疗的疗效并不高,这可能与Ad5载体的低基因转导率有关。随着纤维修饰Ad (Ad5/F35)的发明,Ad的靶转导率得到了提高;然而,需要一种基于Ad5/ f35的基因传递载体系统。因此,我们评估了使用对癌细胞具有高毒性的γδ T细胞作为Ad5/F35载体转运体的可能性。体外实验表明,γδ T细胞比人外周血单核细胞和自然杀伤细胞更有效地表达Ad5/F35载体。此外,他们还可以在体内将载体运输到皮下前列腺癌模型的肿瘤部位。我们得出结论,病毒负载γδ t细胞可能有助于全身癌症病毒治疗。
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