白细胞介素2基因修饰瘤苗治疗胃癌复发转移的初步临床研究

Preliminary clinical trial on immunotherapy with IL-2 gene-modified allogeneic tumor vaccine in recurrent and metastatic gastric cancer patients

目的观察白细胞介素2(IL-2)基因修饰人胃癌细胞瘤苗(HG-1/IL-2)治疗胃癌术后复发和/或转移患者的临床安全性,并初步评价其对患者免疫指标的影响和疗效。方法应用基因工程技术,以逆转录病毒载体将人IL-2cDNA转导入HLA-A2阳性的人胃癌细胞株MKN-45,经60Co照射灭活后,制备成HG-1/IL-2。15例胃癌术后复发/转移患者入组。以5次接种为1疗程,接种时间分别在第1、8、15、29和58天,每次于一侧腹股沟和对侧腋部皮下注射。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免疫学指标和临床受益评价。结果除1例因疾病快速进展,在接种3次后死于多脏器功能衰竭外,余14例均完成5次接种。接种后发热和注射局部红肿、酸胀感是最常见的反应。治疗后未观察到患者血液、肝肾功能等指标的明显异常。部分患者治疗后血清转铁蛋白、免疫球蛋白(Ig)G、IgA、IgM、IL-2等体液免疫和CD3、CD4、CD8等细胞免疫指标有一定程度提高。4例获部分缓解,6例稳定,4例病情进展。结论IL-2基因修饰胃癌细胞瘤苗治疗耐受性好,部分患者体液和细胞免疫指标改善明显。该药物可作为辅助治疗手段,应用于胃癌术后复发转移的综合治疗。

Objective To evaluate the safety,feasibility and potential therapeutic effects of IL 2 gene modified allogeneic gastric cancer vaccine on recurrent and metastatic gastric cancer patients. Methods During the period from March 2002 to March 2003, fifteen patients with recurrent and/or metastatic gastric cancer were enrolled in a special and ongoing phase Ⅰ/Ⅱ clinical trial of this gene modified tumor vaccine. The vaccine was administrated subcutaneously at the first,7th,15th ,28th and 58th day. The toxicity and adverse reactions were observed. The humoral and cellular immune status were evaluated prior to and after 5 vaccinations. Results Fourteen of the 15 patients completed 5 vaccinations. Adverse events consisted of mild to moderate fever,redness and swelling at the site of injection. Only one patient was dropped out after the third injection due to rapidly progressive disease. Hematological and hepatorenal function disturbance were not observed during the immunization. Partial remission was observed in 4 patients, while the disease was stable in 8 patients and progressive in 4. A trend of gradual increase of the humoral and cellular immune parameters could be seen. Conclusions Allogeneic IL 2 gene modified gastric cancer vaccine can improve immune function and be used as adjuvant therapy with good tolerance in the patients with recurrent and metastatic gastric cancer.