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目的 :制备具有内影像特征的抗独特型抗体 ,用于鼻咽癌病人的主动免疫治疗以探讨其抗肿瘤效应。方法 :用杂交瘤技术制备针对Ab1可变区的抗独特型单抗 (Ab2 ) ,免疫同系动物诱导产生免疫应答 ,并用氢氧化铝凝胶沉淀法制成抗独特型疫苗 ,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 2mRNA的表达。结果 :用抗鼻咽癌单抗FC2、HNL5 (Ab1)为免疫原 ,获得了两株抗独特型单抗 2H4和 5D3(Ab2 )。用Ab2免疫小鼠诱导产生了能与相应Ab1竞争结合靶抗原的抗抗独特型抗体 (Ab3)。并能诱发特异性迟发型超敏反应 (DTH)和细胞增殖反应。用Ab2治疗的病人无一例有过敏或其他毒副反应 ,血清中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和IL 2血清水平均未升高。病人血清的IL 2水平含量与PBMCIL 2mRNA的表达呈正相关关系 (r=0 882 9)。结论 :(1) 2H4、5D3具有鼻咽癌相关抗原的内影像 ,能模拟鼻咽癌相关抗原在同系鼠诱导体液和细胞免疫反应。 (2 )疫苗化的
OBJECTIVE: To prepare anti-idiotypic antibodies with internal image features for the active immunotherapy of patients with nasopharyngeal carcinoma to investigate its anti-tumor effect. Methods: Anti-idiotypic monoclonal antibody (Ab2) against Ab1 variable region was prepared by hybridoma technique. The immune homologue was induced to produce immune response. Anti-idiotypic vaccine was prepared by aluminum hydroxide gel precipitation. Radiotherapy of cancer patients for active immunotherapy, 9 cases of radiotherapy and saline injection as a control group, before and after treatment with ELISA test serum antibody and cytokine levels. IL 2 mRNA expression in peripheral blood mononuclear cells (PBMCs) was detected by in situ Northern blotting. Results: Two anti-idiotypic monoclonal antibodies 2H4 and 5D3 (Ab2) were obtained with anti-NPC monoclonal antibody FC2 and HNL5 (Ab1) as immunogens. Immunization of mice with Ab2 induced the production of an anti-idiotypic antibody (Ab3) that competed with the corresponding Ab1 for binding to the target antigen. And can induce specific delayed-type hypersensitivity (DTH) and cell proliferation response. None of the patients treated with Ab2 had allergic or other toxic side effects, serum levels of Ab3 and anti-tumor antibody (Ab1 ’) increased to varying degrees, but human anti-mouse antibody (HAMA) was also produced. Serum cytokines TNFα, IFNγ and IL-2 levels were elevated in most treatment group patients, while serum levels of Ab1 ’, IFNγ, TNFα and IL-2 in the control group were not elevated. There was a positive correlation between IL-2 levels in PBMCs and PBMC IL-2 mRNA expression (r = 0 882 9). Conclusions: (1) 2H4 and 5D3 have the internal images of nasopharyngeal carcinoma-associated antigens, which can simulate the humoral and cellular immune responses induced by nasopharyngeal carcinoma-associated antigens in fellow mice. (2) Vaccinated