Adoptive cell-transfer therapy （ACT） has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, γ9δ2T cells can be activated and expanded in vitroand i...Adoptive cell-transfer therapy （ACT） has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, γ9δ2T cells can be activated and expanded in vitroand in vivoand display strong antitumor activity against colorectal, lung, prostate, ovarian and renal cell carcinomas. However, it is difficult to obtain a large enough number of γδT cells to meet the need for immunotherapy that can overcome the cancer patients＇ immune suppressive tumor microenvironment. In previous studies, our lab confirmed that γ9δ2T cells recognized tumor cells via the CDR3δ region of the γδ-T-cell receptor （TCR）. We constructed full-length human peripheral blood mononuclear cell （PBMC）-derived γ9 and δ2 chains in which the CDR3 region was replaced by an ovarian epithelial carcinoma （OEC）-derived CDR3. We transferred the CDR3δ-grafted γ9δ2TCR into peripheral blood lymphocytes （PBLs） to develop genetically modified γ9δ2T cells. In vitro studies have shown that these CDR3δ-grafted γ9δ2T cells can produce cytokines after stimulation with tumor cell extracts and exhibit cytotoxicity towards tumor cells, including human OEC and cervical adenocarcinoma. CDR3δ-grafted γ9δ2T cells adoptively transferred into nude mice bearing a human OEC cell line demonstrated significant antitumor effects. These results indicate that CDR3δ-grafted γ9δ2T cells might be candidates for clinical tumor immunotherapy.展开更多
目的 探讨重症肌无力(MG)患者T细胞受体(TCR)β链(V β)亚家族优势表达及β链3号互补决定区(CDR3)的长度谱型特点;研究强的松治疗MG患者前后TCR V β优势表达及β链CDR3长度谱型特点的变化。方法 通过逆转录聚合酶链式反应扩增MG患者外...目的 探讨重症肌无力(MG)患者T细胞受体(TCR)β链(V β)亚家族优势表达及β链3号互补决定区(CDR3)的长度谱型特点;研究强的松治疗MG患者前后TCR V β优势表达及β链CDR3长度谱型特点的变化。方法 通过逆转录聚合酶链式反应扩增MG患者外周血循环T细胞中不同亚家族含CDR3的大片段,分析亚家族的表达,并经基因扫描(长度谱型分析)分析CDR3谱型。结果 MG患者外周血TCR Vβ 6、8、12、15亚家族呈倾斜性分布,且部分亚家族T细胞呈现单克隆或寡克隆增殖;强的松治疗后症状明显改善,倾斜性分布现象在缓解期逐渐恢复正常。结论 TCR V β 6、8、12、15亚家族可能与MG症状有关;强的松类肾上腺皮质激素药治疗MG的机制可能是通过改变TCR V β亚家族表达以及抑制病理性T细胞克隆增殖而发挥作用。展开更多
文摘Adoptive cell-transfer therapy （ACT） has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, γ9δ2T cells can be activated and expanded in vitroand in vivoand display strong antitumor activity against colorectal, lung, prostate, ovarian and renal cell carcinomas. However, it is difficult to obtain a large enough number of γδT cells to meet the need for immunotherapy that can overcome the cancer patients＇ immune suppressive tumor microenvironment. In previous studies, our lab confirmed that γ9δ2T cells recognized tumor cells via the CDR3δ region of the γδ-T-cell receptor （TCR）. We constructed full-length human peripheral blood mononuclear cell （PBMC）-derived γ9 and δ2 chains in which the CDR3 region was replaced by an ovarian epithelial carcinoma （OEC）-derived CDR3. We transferred the CDR3δ-grafted γ9δ2TCR into peripheral blood lymphocytes （PBLs） to develop genetically modified γ9δ2T cells. In vitro studies have shown that these CDR3δ-grafted γ9δ2T cells can produce cytokines after stimulation with tumor cell extracts and exhibit cytotoxicity towards tumor cells, including human OEC and cervical adenocarcinoma. CDR3δ-grafted γ9δ2T cells adoptively transferred into nude mice bearing a human OEC cell line demonstrated significant antitumor effects. These results indicate that CDR3δ-grafted γ9δ2T cells might be candidates for clinical tumor immunotherapy.
文摘目的 探讨重症肌无力(MG)患者T细胞受体(TCR)β链(V β)亚家族优势表达及β链3号互补决定区(CDR3)的长度谱型特点;研究强的松治疗MG患者前后TCR V β优势表达及β链CDR3长度谱型特点的变化。方法 通过逆转录聚合酶链式反应扩增MG患者外周血循环T细胞中不同亚家族含CDR3的大片段,分析亚家族的表达,并经基因扫描(长度谱型分析)分析CDR3谱型。结果 MG患者外周血TCR Vβ 6、8、12、15亚家族呈倾斜性分布,且部分亚家族T细胞呈现单克隆或寡克隆增殖;强的松治疗后症状明显改善,倾斜性分布现象在缓解期逐渐恢复正常。结论 TCR V β 6、8、12、15亚家族可能与MG症状有关;强的松类肾上腺皮质激素药治疗MG的机制可能是通过改变TCR V β亚家族表达以及抑制病理性T细胞克隆增殖而发挥作用。
