CS1和钙网蛋白双表达DNA疫苗应用于多发性骨髓瘤免疫治疗的效应及机制研究

CS1是一种最新发现的细胞表面糖蛋白，高度特异性表达于骨髓瘤细胞，在正常组织中未检测到明显的CS1表达，是抗骨髓瘤DNA疫苗非常理想的肿瘤抗原。而最新研究发现钙网蛋白（CRT）的细胞表面表达在肿瘤抗原呈递中具重要作用，能提高MHCⅠ类分子的抗原递呈能力，促进树突状细胞吞噬肿瘤细胞，从而增强肿瘤特异性的CTL。故本课题拟选用CS1作为靶抗原，CRT作为免疫佐剂以增强DNA疫苗的免疫原性，构建双表达CS1和CRT的新型抗骨髓瘤DNA疫苗，以诱导高水平的特异性抗骨髓瘤免疫反应。并拟转入荧光报告基因质粒于小鼠多发性骨髓瘤细胞，构建多发性骨髓瘤小鼠移植瘤模型，采用活体荧光成像评估双表达CS1和CRT的DNA疫苗对小鼠多发性骨髓瘤的治疗效果，探索新的多发性骨髓瘤免疫治疗方式。

CS1 is a cell surface glycoprotein that was recently identified highly expressing on MM cells. There is no apparent CS1 expression detected in normal tissues. So CS1 is a very ideal tumor antigen for the myeloma-specific DNA vaccine. The resent reseach results show that the calreticulin ( CRT ) exposure on the cell surface play a central role in the antigen-presenting pathway. The CRT exposure can improve MHC I molecule to present antigen, facilitate tumor cell recognition by dendritic cells (DC), and elicit tumor-specific cytotoxic T lymphocyte mediated tumor cells elimination. So our research plans to construct a DNA vaccine encoding CS1 linked to calreticulin for the multiple myeloma immunotherapy. This new DNA vaccine applies CS1 as a target MM antigen, CRT as a adjuvant to elicit high level myeloma-specific anti-tumor immune response. Our research also plans to transfer discosomasp red fluorescent protein (DsRed) gene to a mouse myeloma cellline, and construct a mouse multiple myeloma xenograft model. The mouse multiple myeloma xenograft model will be used in vivo fluorescence image analysis system for evaluating the DNA vaccine encoding CS1 linked to calreticulin in treatment of multiple myeloma in mice, to explore one kind of new immunotherapy of multiple myeloma.