Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
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DOI：
10.1182/blood-2007-12-128843
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发表时间：
2008-09-15
期刊：
影响因子：
20.3
通讯作者：
Press, Oliver W.
中科院分区：
文献类型：
--
作者：
Till, Brian G.;Jensen, Michael C.;Press, Oliver W.
用表达肿瘤特异性嵌合T细胞受体的T细胞进行的连续免疫疗法是一种有前景的癌症治疗方法，其先前尚未被探索用于治疗人类受试者中的淋巴瘤。我们报告了一项概念验证临床试验的结果，在该试验中，复发性或难治性惰性B细胞淋巴瘤或套细胞淋巴瘤患者接受了自体T细胞治疗，该T细胞通过电穿孔进行遗传修饰，并携带编码CD 20特异性嵌合T细胞受体和新霉素耐药基因的载体质粒。转染细胞的免疫表型与CD 8（+）效应细胞相似，并在体外显示出CD 20特异性细胞毒性。7名患者共接受了20次T细胞输注，毒性最小。修饰的T细胞在前3名患者体内持续1至3周，他们接受了有限稀释法产生的T细胞，但在接下来的4名患者中持续5至9周，他们接受了大量培养物产生的T细胞，随后接受了14天的低剂量皮下白细胞介素-2（IL-2）注射。在7例接受治疗的患者中，2例维持了先前的完全缓解，1例实现了部分缓解，4例病情稳定。这些结果显示了使用这种方法的过继性T细胞疗法的安全性、可行性和潜在的抗肿瘤活性。该试验在www.clinicaltrials.gov上注册为#NCT00012207。
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. This trial was registered at www.clinicaltrials.gov as #NCT00012207.