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【Blood】应用基因修饰的自体CD20特异性T细胞过继
Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
Brian G. Till1,2, Michael C. Jensen3, Jinjuan Wang1, Eric Y. Chen1, Brent L. Wood4, Harvey A. Greisman4, Xiaojun Qian1, Scott E. James1, Andrew Raubitschek5, Stephen J. Forman6, Ajay K. Gopal1,2, John M. Pagel1,2, Catherine G. Lindgren2, Philip D. Greenberg1,2, Stanley R. Riddell1,2, and Oliver W. Press1,2
1 Clinical Research Division of the Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Department of Medicine, University of Washington, Seattle; 3 Department of Pediatric Hematology-Oncology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA; 4 Department of Laboratory Medicine, University of Washington, Seattle; and 5 Department of Radioimmunotherapy and 6 Division of Hematology and HCT, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA
Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T-cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects. We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T-cell receptor and neomycin resistance gene. Transfected cells were immunophenotypically similar to CD8+ effector cells and showed CD20-specific cytotoxicity in vitro. Seven patients received a total of 20 T-cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections. Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease. These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
应用基因修饰的自体CD20特异性T细胞过继免疫治疗惰性非何杰金淋巴瘤和套细胞淋巴瘤
Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T-cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects.
表达肿瘤特异性嵌合体的T细胞受体的T细胞的过继免疫治疗是一很有前途的肿瘤治疗方法，而在此前没有应用到人淋巴瘤治疗领域。
We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T-cell receptor and neomycin resistance gene.
我们报道了概念证明型临床试验结果，此试验对象为复发或难治的惰性B细胞淋巴瘤或套细胞淋巴瘤患者，通过电孔术将表达CD20特异性嵌合体的T细胞受体和耐新霉素基因的转染质粒基因修饰自体T细胞，并将此淋巴细胞治疗这些患者。
Transfected cells were immunophenotypically similar to CD8+ effector cells and showed CD20-specific cytotoxicity in vitro.
转染细胞与CD8+效应细胞免疫表型特异性相似，体外并显示出CD20特异性细胞毒性。
Seven patients received a total of 20 T-cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections.
7位患者共接受了20次T细胞输注，具有最小细胞毒性。开始的3位患者接受了限制稀释方法产生的T细胞，修饰的T细胞在体内持续了1到3周。后4位患者接受的是成批培养产生的T细胞，接着14天的低剂量皮下IL-2注射，修饰的T细胞持续了5到9周。
Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease.
7个治疗患者，其中2个维持了之前的完全缓解状态，1个获得部分缓解，4个病情稳定。
These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach.
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作者:admin@医学,生命科学 2011-06-11 05:11
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