Li Zeng-Shan, Yang Xin-Wei, Chen Zheng, Dong Hai-Long, Ye Jing, Qu Ping, Lu Shao-Ying, Zhang Xiu-Min, Sui Yan-Fang
Department of Pathology, XiJing Hospital, FMMU, Xi'an, PR China.
Cancer Biol Ther. 2004 Jul;3(7):660-6. doi: 10.4161/cbt.3.7.920. Epub 2004 Jul 9.
Since transfection of established tumors with immunostimulatory genes can elicit antitumor immunity, we treat mouse HCC with in vivo transfection of superantigen SEA and/or costimulatory molecule CD80 and evaluated the safety and efficacy.
Mice with HCC were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin A and/or CD80. Then the mice were evaluated for tumor regression, systemic immunologic responses, survival times and treatment-associated toxicity.
Of all treated mice, the overall response rates (complete or partial remission) for SEA, CD80 and SEA/CD80 treated mice in this study were 65%, 60% and 75% separately, and were significantly higher than that of untreated mice. Most of the treat mice completed the therapy without any significant reaction. CTL activity increased with time of treatment and correlated temporally with an objective tumor response. Also our results indicated that local intratumoral expression of SEA did not lead to detectable deletion or anergy of SEA-reactive spleen T cells. Survival times for hepatoma mice in this study treated by intratumoral injection of SEA, CD80 and SEA/CD80 were prolonged significantly (P < 0.01) compared with the control mice.
由于用免疫刺激基因转染已建立的肿瘤可引发抗肿瘤免疫,我们通过体内转染超抗原SEA和/或共刺激分子CD80来治疗小鼠肝癌,并评估其安全性和疗效。
用脂质复合的编码葡萄球菌肠毒素A和/或CD80的质粒DNA治疗患有肝癌的小鼠。然后评估小鼠的肿瘤消退、全身免疫反应、生存时间和治疗相关毒性。
在所有接受治疗的小鼠中,本研究中SEA、CD80和SEA/CD80治疗组小鼠的总体缓解率(完全或部分缓解)分别为65%、60%和75%,显著高于未治疗小鼠。大多数接受治疗的小鼠完成治疗时没有任何明显反应。CTL活性随治疗时间增加,且在时间上与客观肿瘤反应相关。我们的结果还表明,SEA在肿瘤内的局部表达并未导致可检测到的SEA反应性脾脏T细胞缺失或无反应。与对照小鼠相比,本研究中通过瘤内注射SEA、CD80和SEA/CD80治疗的肝癌小鼠的生存时间显著延长(P < 0.01)。