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Purging with Replication-Selective Adenovirus for the Mixture of Hematopoietic Stem Cells and Tumor Cells

Author: ZhanShu
Tutor: SongSanTai；WuShiKai
School: PLA Military Academy of Medical Sciences
Course: Journal of Clinical Oncology Pharmacology
Keywords: Replication-selective adenovirus Magnetic cell separation Autologous hematopoietic stem cell transplantation Purging in vitro NOD/SCID mouse
CLC: R73-36
Type: PhD thesis
Year: 2006
Downloads: 63
Quote: 0
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Abstract


High-dose chemotherapy (HDC) supported by autologous hematopoietic stem cell transplantation (AHSCT) has gained extensive application as a therapeutic modality in malignant lymphoma and multiple myeloma. Currently it has been under investigation in several malignant solid tumors. From the latest multicenter phaseIII trial, significant improvements in both event-free and overall survival for HDC has achieved in high-risk breast cancer patients.However, tumor cell contamination of autologous stem cell products (autografts) may contribute to relapse.Thus ex vivo purging of tumor cell contaminated autografts may enhance the efficency of AHSCT. Although the magnetic cell separation(MACS) of CD34~+ cell can result in a 2-5 log reduction of tumor cells, one recent data demonstrated that such approach can hardly improve the overall survival.Based on the quantitative difference of coxsackie-adenovirus receptor adenoviral receptor on stem cell and some other malignant tumor cells, a new method mediated by adenovinis to purge the tumor cells from stem cell products has been under inveatigation. A kind of genetically engineered replication-selective adenovinis has been designed for targeting tumor cell. H101 is the prototype for oncolytic adenoviral therapy. In our former study, adenovinis receptor was expressed highly on the surface of breast cancer cell and multiple myeloma cell,while hematopoietic stem cell surface expression was rarely. Meanwhile this was positively correlated with the infectivity of H101.Thus it enlighted us to contrivance a new purging method mediated by H101, and compare the efficiency of H101 with MACS.Firstly we designed a series of methods to detect malignant tumor cells in mimic autogrfts. For breast cancer, RT-PCR amplification of human CK19 specific sequence could detect 10 breast cancer cells in 10~7 peripheral blood mononuclear cells(PBMCs),

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