CAJ | 학술논문

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2H4、5D3,经氢氧化铝凝胶沉淀法制备成抗独特型疫苗Alum-2H4、Alum-5D3,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ELISA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(PBMC)IL-2 mRNA的表达.结果接受Alum-2H4或Alum-5D3治疗的病人无一例有过敏或其他毒副反应,血清中均检测到抗抗独特型抗体(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(HAMA).血清细胞因子TNF-α、IFN-γ和IL-2水平在大多数治疗组病人中升高.而对照组Ab1'、IFN-γ、TNF-α及IL-2血清水平均未升高.病人血清的IL-2含量与PBMC IL-2 mRNA的表达呈正相关关系(r=0.8829).结论 (1)疫苗化的2H4和5D3用于晚期鼻咽癌病人的主动免疫治疗是安全的.(2)抗独特型疫苗可作为模拟抗原激发鼻咽癌病人的主动免疫应答,产生抗肿瘤效应.
목적탐토항독특형역묘주동면역치료비인암병인적항종류효응.방법용량주구유비인암상관항원내영상적항독특형단극륭항체2H4、5D3,경경양화려응효침정법제비성항독특형역묘Alum-2H4、Alum-5D3,대19례만기비인암방료병인작주동면역치료,9례방료가생리염수주사위대조조.용ELISA검측치료전후병인혈청항체화세포인자수평.용원위Northern잡교검측외주혈단개핵세포(PBMC)IL-2 mRNA적표체.결과접수Alum-2H4혹Alum-5D3치료적병인무일례유과민혹기타독부반응,혈청중균검측도항항독특형항체(Ab3)、항종류항체(Ab1')수평균유불동정도적증고,단야산생료인항서항체(HAMA).혈청세포인자TNF-α、IFN-γ화IL-2수평재대다수치료조병인중승고.이대조조Ab1'、IFN-γ、TNF-α급IL-2혈청수평균미승고.병인혈청적IL-2함량여PBMC IL-2 mRNA적표체정정상관관계(r=0.8829).결론 (1)역묘화적2H4화5D3용우만기비인암병인적주동면역치료시안전적.(2)항독특형역묘가작위모의항원격발비인암병인적주동면역응답,산생항종류효응.
Objective To investigate the effect of active immunotherapy with anti-idiotypic vaccine in patients with nasopharyngeal carcinoma (NPC). Methods Anti-idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antigen were used in active immunotherapy in NPC patients receiving radiotherapy. Antibodies and cytokine levels in patient sera were determined using ELISA before and after active immunotherapy. IL-2 mRNA expression in the peripheral blood mononuclear cells (PBMC) was measured by in situ hybridization. Results Nineteen patients with NPC at stage Ⅳ were treated with alum-precipitated 2H4 or 5D3. Neither hypersensitivity nor adverse side effects were observed. The levels of anti-anti-idiotypic antibodies (Ab3) and anti-NPC antibodies (Ab1') were increased. Human anti-mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1' did not increse in the control group. Serum IL-2, IFN-γ and TNF-α levels were increased in most patients in the experimental group, while no differences were observed in Ab1' and cytokine levels between pre- and post-therapy in the control group. In addition, IL-2 mRNA expression in PBMCs from NPC patients was closely related to serum IL-2 (r=+0.8829) levels by in situ hybridization. Conclusions Anti-idiotype vaccine is safe for clinical active immunotherapy. Anti-idiotypic vaccine might be able to enhance humoral and/or cellular immunity in NPC patients receiving radiotherapy.