The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction...The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.展开更多
目的:预测并鉴定乳腺癌相关抗原受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)H-2Kd限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定基础。方法...目的:预测并鉴定乳腺癌相关抗原受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1,ROR1)H-2Kd限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定基础。方法:采用生物信息学方法预测乳腺癌相关抗原ROR1 H-2Kd限制性CTL表位,选取预测软件中评分较高的抗原表位肽进行人工合成及纯化。肽结合试验检测抗原表位肽与H-2Kd分子的亲和力。选用亲和力较高的抗原表位肽体外刺激脾淋巴细胞,ELISA法检测细胞因子γ-干扰素(interferon-γ,IFN-γ)和白介素-12(interleukin-12,IL-12)的分泌。结果:预测的4条候选ROR1 CTL表位肽均具有较高的亲和力,其荧光指数(fluorescence index,FI)在30μg/ml时均大于1.5。ELISA结果显示表位肽ROR1(NYMFPSQGI)可在体外有效诱导IFN-γ和IL-12细胞因子的产生。结论:ROR1(NYMFPSQGI)为乳腺癌相关抗原ROR1H-2Kd限制性CTL表位,为研究以ROR1为靶点的乳腺癌免疫治疗奠定了基础。展开更多
E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respective...E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.展开更多
文摘The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.
基金supported by the grants from National Natural Science Foundation of China(No.81401276,No.81771618 and No.81771662)the Fund Project of Health and Family Planning Commission of Hubei Province(No.WJ2015MA006 and No.WJ2015Q017)
文摘E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.
