重组人p53腺病毒注射液治疗喉癌的Ⅰ期临床试验及追踪观察  

Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: phase Ⅰ clinical trial and follow up

作　　者：韩德民[1] 黄志刚[1] 张伟[1] 于振坤[1] 王琪[1] 倪鑫[1] 陈晓红[1] 潘锦华[1] 王鸿[1] 

机构地区：[1]首都医科大学附属北京同仁医院耳鼻咽喉-头颈外科,北京100015

出　　处：《中华医学杂志》2003年第23期2029-2032,共4页National Medical Journal of China

摘　　要：目的　评价重组人p5 3腺病毒注射液 (rAd p5 3)对喉癌患者的毒理、药理作用。方法将 12例各期喉癌患者随机平分成 3个剂量组 (1× 10 1 0 VP、1× 10 1 1 VP、1× 10 1 2 VP) ;局部注射rAd p5 3,1次 隔日× 5次× 2个疗程 ,经 3年以上的追踪 ,通过症状、体检 (含喉镜检查 )和实验室检查观察其副作用及临床疗效。结果　在 1× 10 1 2 VP组 1例患者出现自限性发热 ,余 11例无异常。所有患者在治疗后常规和重要脏器等检测值均在正常范围。rAd p5 3特异性抗体在治疗后 2～ 3周后转阳性 ;rAd p5 3治疗患者肿瘤组织p5 3蛋白表达明显增强 ;2例患者治疗后SIL 2R水平异常和T细胞亚群失调指标好转 ;所有患者随访 3年以上示无瘤生存。结论　rAd p5 3局部治疗喉癌安全、有效 ,具有广阔的临床应用前景。Objective To evaluate the efficacy and toxicity of recombinant adenovirus p53 injection (SBN-1) in patients with laryngeal cancer. Methods Twelve cases with laryngeal cancer, 11 males and 1 female, aged 59.5±12.4 years, were randomly divided into three groups of 4 patients. The patients received intratumor injection of SBN-1 at the dosage of 1×10 10VP, 1×10 11VP, or 1×10 12VP once every other day for 2 courses of treatment with 5 times of injection as one course of treatment. Two days after the injection the patients were operated on. After the operation SBN-1 of the same doses was injected around the tumor bed. The patients were followed up for more than 3 years by correspondence and out-patient department examinations. ELISA was used to detect the serum anti-adenoviral IgG and IgM, and interleukin-2 receptor (IL-2R). Immunohistochemistry was used to examine the expression of p53 protein in the tumor tissues. Flow cytometry was used to examine the T cell subgroup. The symptoms and side effects were observed. Results One patient in the 10 12VP group presented self-limited fever (38.2～38.6℃) and no other abnormality was observed after the SBN-1 injection. Specific antibody to SBN-1 turned from negative to positive two or three weeks after the first injection. P53 protein expression was significantly enhanced in tumors after injection of SBN-1. The serum level of IL-2R was 750±401 pg/ml before treatment and 552±203 pg/ml after treatment. The numbers of CD3, CD4, and CD8 were 66±10, 41±15, and 32±10 respectively before the treatment and were 67±9, 43±8, and 34±16 respectively after treatment, and the CD4/CD8 ratio was 1.4±0.6 before the treatment and was 1.6±0.9 after treatment. The abnormality in SIL-2R level and the disorder of T cell subgroup were improved in 2 cases. Followed up for over 3 years showed that all cases still lived free of cancer. Conclusion Safe and effective on laryngeal cancer without obvious adverse events, local injection of SBN-1 is a promising treatment.

关 键 词：重组人P53腺病毒 喉癌 临床试验 毒理学 药理作用 P53基因 基因疗法 

分 类 号：R739.62[医药卫生—肿瘤]