白细胞介素-2基因工程人胃癌细胞瘤苗Ⅰ期临床研究  

Phase Ⅰ clinical trial of interleukin-2 gene-modified allogenic gastric cancer cell line for the treatment of far-advanced gastric cancer

作　　者：王克敏[1] 张俊[2] 朱正纲[2] 王秀玲[3] 程枫[1] 燕敏[2] 尹浩然[2] 林言箴[2] 钱关祥[1] 陈诗书[1] 

机构地区：[1]上海第二医科大学人类基因治疗中心,200025 [2]瑞金医院外科上海消化外科研究所 [3]瑞金医院卢湾分院内科

出　　处：《中华消化杂志》2003年第9期523-526,共4页Chinese Journal of Digestion

基　　金：国家自然科学基金 ( 3 9470 792 ) ;国家"863"高科技项目 (BH 0 1 0 4;Z2 0 0 1 0 4;2 0 0 1 AA2 1710 1;Z2 0 0 1 0 4)

摘　　要：目的　评价同种异型 (HLA A2 + )白细胞介素 (IL) 2基因工程人胃癌细胞瘤苗 (HG 1/IL 2 )治疗晚期胃癌的临床安全性并观察其不良反应。方法　应用基因工程技术 ,以逆转录病毒载体介导将人IL 2cDNA转导入人胃癌细胞株MKN 4 5 ,经 10 0Gy60 Co照射灭活后 ,制备成HG 1/IL 2。对 16例晚期胃癌病人施行HG 1/IL 2瘤苗治疗。 5次接种为一疗程 ,接种时间分别在第 1、8、15、2 9和 5 8天 ,每次于一侧腹股沟和对侧腋部皮下注射。剂量分为 4级 ,由初始剂量 1× 10 7/次开始逐级增加 ,每个剂量水平 4例。每次接种后严格观察不良反应 ,并在治疗开始前 1周和治疗结束后进行临床评价 ,同时进行凝血功能、血液生化、肿瘤标记物和相关免疫指标检测。结果　除 1例因疾病属快速进展 ,在接种 3次后死于多脏器功能衰竭外 ,余 15例均完成 5次接种。低热和注射局部红肿、酸胀感是最常见的反应。治疗前后未观察到病人血液学、凝血功能、肝肾功能、血清标志物等指标明显异常。部分病人治疗后血清转铁蛋白、IgG、IgA、IgM ,IL 2等体液免疫指标和CD+ 3 、CD+ 4 、CD+ 8等细胞免疫指标有一定程度提高。结论　在密切观察的前提下 ,HG 1/IL 2基因工程化胃癌细胞瘤苗应用于晚期胃癌的辅助治疗是安全可行的 。Objective To observe the toxicity and adverse reaction of interleukin(IL) 2 gene modified allogenic gastric cancer cell line in far advanced gastric cancer patients. Methods A phase Ⅰ clinical trial was conducted for sixteen far advanced gastric cancer patients with IL 2 gene modified gastric cancer cell line. By gene recombinant technique, human IL 2 cDNA was transfected into human gastric cancer cell line MKN45 via retrovirus based vector.These cells were then inactivated by irradiation (100 Gy) and were cryopreserved for the vaccine. The immunization were administrated subcutaneously at the first, 8 th , 15 th , 29 th and 58 th day. The patients were divided into 4 dosage groups, which the dosage of the vaccine was administrated in each subsequent level. The toxicity and adverse reaction were evaluated by WHO criteria. Results Fifteen of the 16 patients completed the immunization. Side effects of treatment consisted of mild to moderate fever, redness and swelling at the site of injection, which were the most common symptoms. Only one patient abandoned after the third injection due to rapidly progressive disease. Other reactions including allergic shock, bone marrow depression and disturbance of hepatorenal function were not observed during the immunization.In some patients, the serum transferrin, humoral immune parameters such as IgG, IgA, IgM,IL 2 and cellular immune parameters such as CD + 3,CD + 4,CD + 8 had been improved after treatment.Conclusions This trial demonstrates the feasibility, safety and potential therapeutic effects of vaccination of gastric cancer patients with allogenic, gene modified gastric cancer cell line. The dosage of the vaccine recommended for phase Ⅱ clinical trail is 5×10 7 cells per time.

关 键 词：白细胞介素-2 基因工程 胃癌 瘤苗 临床研究 

分 类 号：R735.2[医药卫生—肿瘤]