首页 | 本学科首页   官方微博 | 高级检索  
     


Transduction of the Macrophage Colony-stimulating Factor Gene into Human Multidrug Resistant Cancer Cells: Enhanced Therapeutic Efficacy of Monoclonal Anti-P-glycoprotein Antibody in Nude Mice
Authors:Saburo Sone  Takashi Tsuruo  Shigeo Sato  Seiji Yano  Yasuhiko Nishioka  Tsutomu Shinohara
Affiliation:Third Department of Internal Medicine, Tokushima University School of Medicine, 3-18-15 Kuramotocho, Tokushima 770;Institute of Molecular and Cellular Biosciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo;Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170
Abstract:To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antihody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) and high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.
Keywords:Anti-P-glycoprotein antibody    Multidrug resistance    M-CSF    Gene therapy
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号