多发性骨髓瘤基因修饰瘤苗诱导体内抗肿瘤反应的实验研究论文.docVIP

　　多发性骨髓瘤基因修饰瘤苗诱导体内抗肿瘤反应的实验研究论文 .freelyeloma (MM) remains an incurable malignancy despite advances in chemotherapy. Myeloablative chemotherapy folloatopoietic stem cell transplantation has increased the incidence of plete remission，but almost all patients achieving plete remission ultimately experience relapse［1-3］. Because these chemotherapies have only limited value，alternative strategies are needed to solve these problems. Immunotherapy may represent a means of maintaining plete remission. Based on the fact that myeloma cells contain a multitude of tumor antigens that can effectively stimulate antitumor T cells，several investigators have repor- ted immunotherapeutic approaches via inoculating mye- This project ent Grants ’973’ (No. 2004CB518801 and No. 2002 CB713804)，Chinese High-Tech Program ’863’ (No. 2003AA216050) and Chinese National Science Foundation (No. Corresponding author: edicine. loma cell lysates，yeloma cells or geically modified myeloma cell vaccines to augment the immunogenicity of myeloma cells. Numerous applications of genes encoding tumor suppressive proteins，cytokines and costimulatory molecules have been proposed in cancer (including MM) therapy［4-7］. Although the results of most preclinical investigations carried out in vitro and in mouse models or-specific antigen，myeloma cells escape from immune surveillance mainly by doulatory molecules and inhibiting induction and maturation of dendritic cells (DCs)［6，10-11］. Hence a bination of immune-stimulating genes should be more efficient than any single gene. In previous study，onstrated that yeloma cell vaccination co-transferred an ediated by rebinant adenovirus Ad-p53/GM-CSF/B7-1 induces allologous and autologous specific anti-tumor cytotoxicity in vitro［12］. In this study ediated immunity is protective against subsequent tumor challenge. NOD/SCID mice are the most immunodeficient of the SCID variants，and are the most supportive host for human stem cells［13］. Most SCID mouse myeloma