GM-CSF修饰的异体肿瘤细胞疫苗治疗晚期肿瘤的Ⅰ期临床试验  

Phase I clinical trial of granulocyte macrophage colony-stimulating factor-secreting allogeneic cellular immunotherapy for advanced cancer

作　　者：康红刚[1] 王运良[1] 于津浦[1] 曹水[1] 任宝柱[1] 张新伟[1] 张维红[1] 韩颖[1] 任秀宝[1] 

机构地区：[1]天津医科大学附属肿瘤医院生物治疗科,300060

出　　处：《中国医药生物技术》2008年第6期420-424,共5页Chinese Medicinal Biotechnology

基　　金：天津市科技创新专项资金(06FZZDSF01500)

摘　　要：目的探讨GM-CSF修饰的异体肿瘤细胞疫苗的安全性和临床有效性。方法收录我院2007年1月至2008年5月病理明确的IV期癌症患者50例,其中恶黑11例,卵巢癌10例,肾癌15例,胃癌/结直肠癌14例。每周皮下注射肿瘤细胞和GM-CSF分泌细胞混合物1ml;共受6次。在第1、5次注射同时,进行DTH接种试验。治疗前后取外周血样进行淋巴细胞亚型及细胞因子检测。治疗完成1个月后进行影像学检查。结果所有患者对治疗耐受良好,无脱组患者。主要不良反应为,注射局部的红肿疼痛,硬结,瘙痒和发热。4例治疗后影像学好转但未达到部分缓解,32例稳定,14例进展。DTH阳性率68%(34/50)。流式细胞仪检测治疗后CD8+T细胞(CTL)明显增加(P<0.05),CD4+CD25+CD127–T细胞(Treg)降低(P<0.05)。ELISA检测IFN-γ治疗前后的变化无统计学意义,但有升高趋势。结论异体GM-CSF肿瘤疫苗免疫治疗安全,耐受良好,能改善患者的机体免疫状态。Objective To evaluate the clinical safety and efficacy of GM-CSF-modified allogeneic cellular vaccine. Methods Fifty stage IV patients were definitely diagnosed pathologically as malignant melanoma （n = 11）, ovarian cancer （n = 10）, renal cell carcinoma （n = 15）, gastric/colonic carcinoma （n = 14）. Treatment was administered weekly via subcutaneouly injections of vaccinations for 6 weeks. At the first and fifth vaccine injections, DTH test were performed. The lymphocyte subtype and cytokine of the peripheral blood were tested at both pre-treatment and post-treatment. The imaging examination was made one month later. Results All the patients completed the trial. The toxicities included local injection-site reactions and fever. Four had mixed responses, 32 were stable and 14 showed progression. DTH positive rate was 68% （34/50）. All categories had CD8＋T cell （CTL） significantly increased （P = 0.000） and CD4＋CD25＋CD127-T cell （Treg） significantly decreased （P 〈 0.05）. 1FN showed a rising trend in all the patients. Conclusion This allogeneic cancer immunotherapy has favorable safety and tolerance profile and it is immunologically active.

关 键 词：癌症疫苗 肿瘤转移 粒细胞巨噬细胞 集落刺激因子 

分 类 号：R730.5[医药卫生—肿瘤]