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用于调节移植物抗白血病效应的自杀基因转导T细胞

Suicide-gene-transduced T-cells for the regulation of the graft-versus-leukemia effect.

作者信息

Bonini C, Ciceri F, Marktel S, Bordignon C

机构信息

Telethon Institute for Gene Therapy (TIGET), Milano, Italy.

出版信息

Vox Sang. 1998;74 Suppl 2:341-3. doi: 10.1111/j.1423-0410.1998.tb05440.x.

DOI:10.1111/j.1423-0410.1998.tb05440.x
PMID:9704465
Abstract

In allogeneic marrow transplantation (BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-vs-host disease (GvHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. In the first pilot study, infusions of donor lymphocytes transduced with the Herpes Simplex virus thymidine kinase (HSV-tk) suicide resulted in anti-tumor activity in 50% of patients. Acute GvHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. If these results will be confirmed in larger studies, genetic manipulation of donor lymphocytes will increase efficacy and safety of allogeneic marrow transplantation.

摘要

在异基因骨髓移植(BMT)中,供体淋巴细胞在移植物抗白血病和免疫重建中都发挥着核心治疗作用。然而,其应用受到严重移植物抗宿主病(GvHD)风险的限制。人们已经研究了不同策略,以在避免GvHD风险的同时获得供体淋巴细胞带来的所有益处。在首个初步研究中,用单纯疱疹病毒胸苷激酶(HSV-tk)自杀基因转导的供体淋巴细胞输注使50%的患者产生了抗肿瘤活性。更昔洛韦诱导转导细胞消除可有效控制急性GvHD。如果这些结果能在更大规模研究中得到证实,对供体淋巴细胞进行基因操作将提高异基因骨髓移植的疗效和安全性。

相似文献

1
Suicide-gene-transduced T-cells for the regulation of the graft-versus-leukemia effect.用于调节移植物抗白血病效应的自杀基因转导T细胞
Vox Sang. 1998;74 Suppl 2:341-3. doi: 10.1111/j.1423-0410.1998.tb05440.x.
2
Human HLA-specific T-cell clones with stable expression of a suicide gene: a possible tool to drive and control a graft-versus-host- graft-versus-leukemia reaction?稳定表达自杀基因的人源HLA特异性T细胞克隆:驱动和控制移植物抗宿主-移植物抗白血病反应的一种可能工具?
Blood. 1996 Aug 1;88(3):1098-103.
3
HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.将单纯疱疹病毒胸苷激酶基因导入供体淋巴细胞以控制异基因移植物抗白血病作用
Science. 1997 Jun 13;276(5319):1719-24. doi: 10.1126/science.276.5319.1719.
4
Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: clinical follow-up and improved new vectors.单纯疱疹病毒胸苷激酶基因转移用于可控性移植物抗宿主病和移植物抗白血病:临床随访及改良新载体
Hum Gene Ther. 1998 Oct 10;9(15):2243-51. doi: 10.1089/hum.1998.9.15-2243.
5
Suicide-gene-Transduced donor T-cells for controlled graft-versus-host disease and graft-versus-tumor.用于可控移植物抗宿主病和移植物抗肿瘤的自杀基因转导供体T细胞
Int J Hematol. 2002 Nov;76(4):305-9. doi: 10.1007/BF02982688.
6
Preemptive control of graft-versus-host disease in a murine allogeneic transplant model using retrovirally transduced murine suicidal lymphocytes.在小鼠同种异体移植模型中,使用逆转录病毒转导的小鼠自杀性淋巴细胞对移植物抗宿主病进行抢先控制。
Cancer Res. 2001 Apr 15;61(8):3355-60.
7
Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation.将单纯疱疹病毒胸苷激酶(HSV-tk)基因转入供体外周血淋巴细胞,用于异基因骨髓移植后对供体抗肿瘤免疫进行体内调节。
Hum Gene Ther. 1995 Jun;6(6):813-9. doi: 10.1089/hum.1995.6.6-813.
8
Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified, remain fully functional, and are killed efficiently with ganciclovir.胸苷激酶(TK)基因转导的人淋巴细胞能够被高度纯化,保持完全功能,并能被更昔洛韦有效杀伤。
Blood. 1997 Feb 15;89(4):1334-40.
9
Kinetics of in vivo elimination of suicide gene-expressing T cells affects engraftment, graft-versus-host disease, and graft-versus-leukemia after allogeneic bone marrow transplantation.体内表达自杀基因的T细胞清除动力学影响异基因骨髓移植后的植入、移植物抗宿主病和移植物抗白血病效应。
J Immunol. 2004 Sep 15;173(6):3620-30. doi: 10.4049/jimmunol.173.6.3620.
10
Prophylaxis of graft-versus-host disease by lentiviral-mediated expression of herpes simplex virus-thymidine kinase and ganciclovir treatment.通过慢病毒介导的单纯疱疹病毒胸苷激酶表达及更昔洛韦治疗预防移植物抗宿主病
Transplant Proc. 2008 Oct;40(8):2665-9. doi: 10.1016/j.transproceed.2008.08.063.

引用本文的文献

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Forkhead-Box-P3 Gene Transfer in Human CD4 T Conventional Cells for the Generation of Stable and Efficient Regulatory T Cells, Suitable for Immune Modulatory Therapy.将叉头框蛋白P3基因导入人CD4传统T细胞以产生稳定且高效的调节性T细胞,适用于免疫调节治疗。
Front Immunol. 2017 Oct 12;8:1282. doi: 10.3389/fimmu.2017.01282. eCollection 2017.
2
Editorial: Improving the safety of cell therapy products by suicide gene transfer.社论:通过自杀基因转移提高细胞治疗产品的安全性
Front Pharmacol. 2015 Aug 25;6:174. doi: 10.3389/fphar.2015.00174. eCollection 2015.
3
Genetically modified donor leukocyte transfusion and graft-versus-leukemia effect after allogeneic stem cell transplantation.
基因修饰供者白细胞输注和异基因干细胞移植后的移植物抗白血病效应。
Hum Gene Ther. 2011 Jul;22(7):829-41. doi: 10.1089/hum.2010.162. Epub 2011 Mar 30.
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Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors.来自部分人类白细胞抗原(HLA)不匹配(HLA单倍型相同)相关供者的造血干细胞移植。
Bone Marrow Transplant. 2008 Sep;42(6):365-77. doi: 10.1038/bmt.2008.215. Epub 2008 Aug 4.
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Suicide-gene-Transduced donor T-cells for controlled graft-versus-host disease and graft-versus-tumor.用于可控移植物抗宿主病和移植物抗肿瘤的自杀基因转导供体T细胞
Int J Hematol. 2002 Nov;76(4):305-9. doi: 10.1007/BF02982688.