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一种基于单纯疱疹病毒2型的溶瘤病毒可作为一种吸引剂,引导过继转移的T细胞迁移至肿瘤部位。

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites.

作者信息

Fu Xinping, Rivera Armando, Tao Lihua, Zhang Xiaoliu

机构信息

Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Texas, USA.

Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.

出版信息

Oncotarget. 2015 Jan 20;6(2):902-14. doi: 10.18632/oncotarget.2817.

Abstract

Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.

摘要

过继性T细胞疗法已显示出在癌症治疗方面的前景。然而,对于实体瘤的治疗,需要提高过继转移的T细胞归巢至肿瘤部位的能力。我们探讨了使用源自单纯疱疹病毒2型(HSV-2)的溶瘤病毒作为过继转移T细胞迁移的局部吸引剂的可能性,这种病毒能够主动将T效应细胞吸引至感染部位。我们的数据表明,瘤内注射这种病毒确实能够吸引过继转移的T细胞向治疗的肿瘤部位进行活跃迁移。此外,一旦被病毒吸引至肿瘤部位,T细胞在那里持续存在的时间明显长于未处理的肿瘤。趋化因子分析表明,在病毒处理的肿瘤中,CXCL9和CXCL10以及其他几种属于炎症趋化因子家族的趋化因子显著升高。这些趋化因子最初引导T细胞迁移至肿瘤部位,然后维持它们在肿瘤部位的持续存在,从而导致显著增强的治疗效果。我们的数据表明,这种病毒疗法可与过继性T细胞疗法联合使用,以增强其对实体瘤的治疗效果,否则单独使用该疗法难以治疗实体瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba67/4359264/99917ab158f6/oncotarget-06-902-g001.jpg

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