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您的检索式：作者名="Kevin T MCDONAGH"
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| 1 | Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2显示文摘We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2. | 杨建民 Michael S FRIEDMAN Christopher M REYNOLDS Marianne T HUBEN Lee WILKE Jennifer FULLER 李桥 Zelig ESHHAR James J MULE Kevin T MCDONAGH | 2004 | Journal of Microbiology and Immunology2004，2，4： | 5 |
| 2 | In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene显示文摘We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells. | JIAN MIN YANG MICHAEL S FRIEDMAN MARIANNE T HUBEN JENNIFER FULLER QIAO LI ALFRED E CHANG JAMES J MULE KEVIN T MCDONAGH | 2006 | Journal of Microbiology and Immunology2006，4，2： | 3 |
| 3 | 转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用显示文摘目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(SK-OV-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。 | 杨建民 Michael S Friedman 李峤 James J Mule Alfred E Chang Kevin T McDonagh | 2006 | 中国肿瘤生物治疗杂志2006，13，4： | 2 |
| 4 | T淋巴细胞的基因修饰及其在肿瘤治疗中的应用显示文摘异基因造血干细胞移植后供体淋巴细胞输注治疗恶性血液病的成功进一步增强了人们应用细胞免疫治疗恶性肿瘤的信心。但从每一位患者体内克隆出肿瘤细胞特异性的CTL,并在体外扩增到足够的细胞数量后回输体内是一项十分费时费力的工作,也很不经济。近些年人们尝试应用逆转录病毒介导的基因转染技术对T淋巴细胞进行基因修饰,以增强T淋巴细胞对肿瘤细胞的靶向性,在体内、体外均取得了令人鼓舞的成果。本文将简要介绍通过病毒转染以肿瘤抗原特异性TCR、嵌合性TCR修饰T淋巴细胞的方法,基因修饰后淋巴细胞的抗肿瘤作用的发生机制以及动物体内实验结果。对逆转录病毒修饰T淋巴细胞所带来的潜在危险性及对策也进行了讨论。 | 杨建民 Kevin T MCDONAGH | 2007 | 中国肿瘤生物治疗杂志2007，14，4： | 0 |
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