用抗独特型疫苗主动免疫治疗鼻咽癌病人的临床研究  

Clinic study of active immunotherapy with anti idiotypic vaccine for patients of nasopharyngeal carcinoma(NPC)

作　　者：李官成[1] 谢鹭[1] 周国华[1] 符红普[2] 周建华[3] 孙去病[1] 

机构地区：[1]湖南医科大学肿瘤研究所,长沙410078 [2]湖南省肿瘤医院放疗科,长沙410006 [3]湖南医科大学病理教研室,长沙410078

出　　处：《癌症》1999年第4期372-375,共4页Chinese Journal of Cancer

基　　金：国家自然科学基金;美国中华医学基金会( C M B) 资助

摘　　要：目的：探讨抗独特型疫苗主动免疫治疗鼻咽癌病人的抗肿瘤效应。方法：用两株具有鼻咽癌相关抗原内影像的抗独特型单克隆抗体２ Ｈ４ 、５ Ｄ３ ，经氢氧化铝凝胶沉淀法制备成抗独特型疫苗 Ａｌｕｍ２ Ｈ４ 、 Ａｌｕｍ５ Ｄ３ ，对１９ 例晚期鼻咽癌放疗病人作主动免疫治疗，９ 例放疗加生理盐水注射为对照组。用 Ｅ Ｌ Ｉ Ｓ Ａ 检测治疗前后病人血清抗体和细胞因子水平。用原位 Ｎｏｒｔｈｅｒｎ 杂交检测外周血单个核细胞（ Ｐ Ｂ Ｍ Ｃ） Ｉ Ｌ２ ｍ Ｒ Ｎ Ａ 的表达。结果： 接受 Ａｌｕｍ２ Ｈ４ 或 Ａｌｕｍ５ Ｄ３ 治疗的病人无一例有过敏或其他毒副反应， 血清中抗抗独特型抗体（ Ａｂ３） 、抗肿瘤抗体（ Ａｂ１’） 水平均有不同程度的增高，但也产生了人抗鼠抗体（ Ｈ Ａ Ｍ Ａ） 。血清细胞因子 Ｔ Ｎ Ｆα、 Ｉ Ｆ Ｎγ和 Ｉ Ｌ２ 水平在大多数治疗组病人中升高。而对照组 Ａｂ１＇ 、 Ｉ Ｆ Ｎγ、 Ｔ Ｎ Ｆα及 Ｉ Ｌ２ 血清水平均未升高。病人血清的 Ｉ Ｌ２ 含量与 Ｐ Ｂ Ｍ Ｃ Ｉ Ｌ２ ｍ Ｒ Ｎ Ａ 的表达呈正相关关系（ｒ＝ ０．８８２９） 。结论：（１） 疫苗化的２ Ｈ４ 和５ Ｄ３ 用于晚期鼻咽癌病人的主动免疫治疗是安全的。（２）Objective:To investigate active immunotherapy with anti idiotypic vaccine for patients with nasopharygeal carcinom(NPC).Method:Anti idiotypic antibodies(2H4/5D3) bearing the internal image of the NPC antigen were used in active immunotherapy to NPC patients receiving radiotherapy.Using ELISA, antibodies and cytokine levels in patients’sera were determined before and after active immunotherapy.IL 2 mRNA expression in peripheral blood mononuclear cell (PBMC) were measured as well by in situ hybridization.Results:Nineteen patients with NPC at stage Ⅳwere treated with Alum precipitated 2H4 or 5D3.Neither hypersensitivity nor adverse side effect was observed.Anti anti idiotypic antibodies(Ab3)were elevated,the levels of anti NPC antibodies(Ab1')were increased and human anti mouse antibodies (HAMA) were occurred in nineteen patients of the experimental group,whereas the levels of Ab1'didn't rise in control group.Serum IL 2,IFN γand TNF αlevels were increased in most patients in experimental group.While in the control group,there was no difference of Ab1' and cytokine level between pre therapy and post therapy,in addition,IL 2 mRNA expression in PBMC of NPC patients was closely related to serum IL 2(r=+0.8829)by in situ hybridization.Conclusions:(1)Anti idiotype vaccine is safe for clinic active immunotherapy.(2)Anti idiotypic vaccine might enhance humoral and/or cellular immunity of NPC patients receiving radiotherapy.

关 键 词：鼻咽肿瘤 抗独特型疫苗 主动免疫治疗 

分 类 号：R739.630.5[医药卫生—肿瘤] R730.51[医药卫生—临床医学]