MUC1-2VNTR基因免疫治疗多发性骨髓瘤荷瘤小鼠的实验研究  

MUC1-2VNTR DNA Vaccine Induces Immune Responses in Mouse Model with Multiple Myeloma

作　　者：刘月波[1] 周泽平[1] 王浩[2] 杨红[1] 牟红[1] 黄桂云 张铀[1] 

机构地区：[1]昆明医科大学第二附属医院血液科,云南昆明650101 [2]山东大学齐鲁医院输血科,山东济南250012

出　　处：《中国实验血液学杂志》2015年第5期1366-1369,共4页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目(30760080)

摘　　要：目的:明确粘蛋白1两串联重复区(MUC1-2VNTR)基因疫苗对多发性骨髓瘤荷瘤BALB/c小鼠的治疗效果。方法:用转染pcDNA3.1-MUC1的P3X63Ag8.653小鼠骨髓瘤细胞皮下接种以建立BALB/c荷瘤小鼠模型。用含MUC1-2VNTR的重组质粒pcDNA3.1-2VNTR/myc-hisB肌肉注射免疫小鼠,采用乳酸脱氢酶法检测细胞毒性T细胞(CTL)反应活性,CCK-8法检测脾淋巴细胞增殖活性。观察小鼠的抑瘤率,肿瘤质量。结果:用重组质粒免疫BALB/c荷瘤小鼠25 d后,重组质粒组肿瘤质量明显轻于空质粒对照组(0.5605±0.2065 g vs.1.521±0.6985g)(P<0.01)。重组质粒肌肉注射组CTL、NK细胞活性显著高于对照组;小鼠脾淋巴细胞得到增殖,与空质粒对照组比较,差异非常显著(P<0.01)。MUC1-2VNTR基因免疫能诱发小鼠抗肿瘤作用。结论:MUC1-2VNTR基因疫苗可针对多发性骨髓瘤荷瘤BALB/c小鼠诱导产生特异性细胞及体液免疫应答,能诱发小鼠抗肿瘤效应,对多发性骨髓瘤的治疗具有潜在的应用价值。Objective: To investigate the humoral and cellular immune responses induced by MUC1-2VNTR DNA vaccine in multiple myeloma( MM) tumor-bearing mice. Methods: In vitro,multiple myeloma cells were transfected by plasmid pcDNA3. 1-2VNTR/myc-hisB with Lipofectamine2000. The above-mentioned mouse myeloma cells were inoculated subcutaneously into female BALB /c mice for establishing tumor-bearing animal models. These female BALB /c mice were immunized with pcDNA-2VNTR/myc-hisB or pcDNA /myc-hisB. The cytotoxic T lymphocyte( CTL) activity was detected by the LDH method and the spleen lymphocyte proliferation activity was detected by CCK-8 method. Results: After immunization of BALB /c tumor-bearing mice with recombinant plasmid for 25 days,the tumor mass( 0. 5605 ± 0. 2065 g) was significantly lighter than that in the empty plasmid control group( 1. 521 ±0. 6985 g)( P < 0. 01) and the control group( 1. 5315 ± 0. 5425 g)( P < 0. 01). The difference of tumor mass was not statislically significant between empty plasmid control group( 1. 521 ± 0. 6985 g) and the control group( 1. 5315 ±0. 5425 g)( P > 0. 05). The CTL and NK cell activity was significantly higher in the group of intramuscular injection with recombinant plasmid than that in control group. The spleen lymphocyte proliferation was statistically significantly increased after being immunized with recombinant plasmid pcDNA3. 1-2VNTR/myc-hisB,compared with empty vector( P < 0. 01). The results showed that MUC1-2VNTR gene immunization could induce anti-tumor effect in MM tumorbearing mice. Conclusion: MUC1-2VNTR DNA immunization can elicit both humoral and cellular tumor specific immune response to multiple myeloma in MM tumor-bearing mice. It suggested that the MUC1-2VNTR DNA vaccine may be a potential treatment measure for patients with MM.

关 键 词：多发性骨髓瘤 两串联重复区基因疫苗 基因疫苗 

分 类 号：R733.3[医药卫生—肿瘤]