跨膜型超抗原金黄色葡萄球菌肠毒素A融合蛋白的抗肿瘤作用  

Antitumor effects of the fusion protein of transmembrane-staphylococcal enterotoxin A

作　　者：马文学[1] 余海[1] 王青青[2] 金洪传[1] 鲍建芳[3] 易平勇[1] 黄常新[2] 李经忠[2] 

机构地区：[1]浙江大学肿瘤研究所,浙江杭州310031 [2]浙江大学免疫学研究所,浙江杭州310031 [3]浙江大学医学院细胞与分子生物学实验中心,浙江杭州310031

出　　处：《中国药理学与毒理学杂志》2003年第6期426-431,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目 (39770 837);浙江省自然科学基金资助项目(399131;30 15 80 )~~

摘　　要：目的　为扩大超抗原金黄色葡萄球菌肠毒素A(SEA)的抗瘤谱 ,制备跨膜型SEA融合蛋白 ,研究该蛋白制备的肿瘤疫苗的抗肿瘤作用。方法　在荷B16黑色素瘤的C5 7BL/ 6小鼠上 ,观察跨膜型SEA融合蛋白制备的肿瘤疫苗对荷瘤小鼠的免疫治疗作用和免疫保护作用 ,并通过乳酸脱氢酶 (LDH)释放法检测治疗组和免疫组小鼠脾细胞的天然杀伤细胞(NK)和细胞毒性T细胞 (CTL)活性。结果　融合蛋白制备的肿瘤疫苗能够显著抑制荷瘤小鼠肿瘤的生长 ,并延长其生存期 ,其脾细胞的NK和CTL活性显著增强。同时 ,该肿瘤疫苗对同种肿瘤细胞攻击可产生较强的免疫保护作用。结论　跨膜型SEA融合蛋白制备的肿瘤疫苗具有显著的抗肿瘤作用 ,可有效激发荷瘤小鼠机体的特异性和非特异性抗肿瘤免疫应答 ,增强CTL和NK活性。AIM To prepare transmembrane staphylococcal enterotoxin A fusion protein(TM SEA) vaccine and to study its antitumor effect and the related mechanism. METHODS The B16 melanoma model of C57BL/6 mice was established, the antitumor effect and the protective immunity elicited by the B16 TM SEA tumor vaccine were investigated, the natural killer(NK) and cytotoxicity T lymphocytes(CTL) activity of the splenocytes derived from the treated and immunized mice were measured by LDH release assay. RESULTS Tumor growth was inhibited and the survival time prolonged significantly in melanoma bearing mice treated with the B16 TM SEA tumor vaccine. The NK and CTL activity of splenocytes derived from the mice treated with the B16 TM SEA vaccine increased significantly as compared with those in controls. Immunization of the mice with the B16 TM SEA vaccine elicited protective immunity against the following tumor challenge of B16 cells. Higher CTL activity was induced in vaccinated mice than that in unvaccinated mice. CONCLUSION The tumor vaccine based on TM SEA fusion protein could elicit strong antitumor effect through more efficient induction of specific and nonspecific antitumor immune responses. This tumor vaccine may be as an efficient approach used for the treatment of cancer recurrence and micro metastasis.

关 键 词：超抗原 跨膜 融合蛋白 免疫疗法 T淋巴细胞 

分 类 号：R73-36[医药卫生—肿瘤]