重组鼠CD40配体的Ankara痘病毒疫苗对鼠淋巴瘤的免疫治疗作用的研究  

The research of immunotherapeutic effect of recombinant Ankara virus encoding murine CD40L in mu- fine B -cell lymphoma

作　　者：赵丽娜[1] 全丽娜[1] 郭秀臣[1] 刘爱春[1] 

机构地区：[1]哈尔滨医科大学附属肿瘤医院血液淋巴内科,哈尔滨10081

出　　处：《实用肿瘤学杂志》2013年第4期308-312,共5页Practical Oncology Journal

基　　金：2009年黑龙江省自然科学基金面上项目（D200939）;2009年哈尔滨市科技创新人才研究专项资金项目（2009RFLXS005）

摘　　要：目的研究Ankara痘病毒和mCIMOL的重组体TBC-MVA-mCD40L对小鼠淋巴瘤的免疫治疗作用。方法应用流式细胞术检测经体外或者体内转染mCD40L的A20瘤细胞的表面共刺激分子CD80和CD86的表达。构建了BALB／c小鼠的B细胞淋巴瘤模型并分组接受瘤内注射TBC—MVA—mCD40L联合系统化疗的治疗模式。另外，应用与A20细胞孵育后的TBC-MVA-mCD40L对鼠进行免疫，观察其对鼠淋巴瘤的预防作用。通过观察小鼠接种的肿瘤的大小和生长情况来判断治疗效果。结果转染CIMOL后流式检测A20细胞表面共刺激分子CD80和CD86的表达增强。TBC—MVA—mCIMOL免疫治疗联合化疗能成功地使肿瘤消退并使荷瘤鼠获得长期生存。TBC-MVA-mCD40L免疫预防接种能使小鼠获得长期的抗肿瘤免疫。结论对B淋巴瘤细胞的CD40L基因修饰策略能有效增强机体的对抗B细胞淋巴瘤的系统免疫，为将来B细胞淋巴瘤患者肿瘤内注射TBC—MVA—mCD40的免疫治疗和预防方法提供依据，为该免疫治疗方法的临床应用奠定基础。Objective In this study,we investigated the therapeutic antitumor effect of recombinant An- kara virus encoding murine CD40L（ TBC -MVA -mCD40L）in a murine B -cell lymphoma model. Methods After infection in vitro and in vivo, costimulatory molecules CD80 and CD86 expressions of A20 cells were as- sessed by flow cytometry. BALB/c mice with established s. c. and widely metastatic A20 lymphoma tumors were treated with intratumoral injections of TBC - MVA - mCD40L together with systemic chemotherapy. Next the BALB/c mice were vaccinated with irradiated A20 cells transduced with TBC - MVA - mCD40L before rechal- lenged with A20 and another CT26 cell line. We observed direct antitumor effect and prophylactic antitumor pro- tection effect of TBC - MVA - mCD40L by measuring the tumor size of lymphoma model（A20） in BALB/c mice. Results Some tumor cells in the injected sites expressed the CD40L transgene,and had increased expressions of the CD80 and CD86 costimulatory molecules. The combined chemoimmunotherapy resulted in complete tumor re- gression and long - term survival of the mice. Otherwize, mice vaccinated with irradiated A20 cells transduced with TBC - MVA - mCD40L are protected against A20 tumor cells, Conclusion These results show that genetic modification of tumor B cells with CD40L can be a useful strategy to promote systemic immunity against B - cell malignancies. The results support future plans for intratumoral injection of TBC - MVA - mCD40L in patients with lymphoma.

关 键 词：CD40配体 淋巴瘤 免疫治疗 

分 类 号：R733[医药卫生—肿瘤]