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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.

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.