Centre for Immune Regulation, Institute of Immunology, University of Oslo and Rikshospitalet Oslo University Hospital Section of Hematology, Medical Department, Rikshospitalet Oslo University Hospital, Oslo, Norway.
Eur J Haematol. 2011 May;86(5):385-95. doi: 10.1111/j.1600-0609.2011.01590.x. Epub 2011 Mar 30.
A homodimeric fusion DNA vaccine targeting idiotype (Id) to antigen-presenting cells (APC) induced robust tumor protection in a mouse model of multiple myeloma (MM). Similar Id vaccine molecules were generated for four patients with MM with three main objectives: (i) do the vaccine molecules induce bona fide anti-Id immune responses in mice? (ii) does targeting of the vaccine molecules to APC enhance immune responses? (iii) can anti-Id antibodies, generated as by-product in vaccinated mice, be used to establish sensitive assays for complete remission (CR) prior to patient vaccination?
Chimeric vaccine molecules targeting patient Id to mouse major histocompatibility complex (MHC) class II molecules were genetically constructed for four patients with MM.
DNA vaccination of mice with chimeric vaccines targeting patient Id to mouse MHC class II molecules elicited antibodies specific for the patient's myeloma protein. Targeting MHC class II greatly enhanced anti-Id responses. Mouse anti-Id antibodies were used to establish myeloma protein-specific enzyme-linked immunosorbent assays (ELISAs) that were between 75 and 1500 times more sensitive than conventional serum protein electrophoresis and immunofixation.
These results pave the way for testing targeted DNA Id vaccines in patients in CR. Id- and patient-specific ELISA could be established affording evaluation of CR depth beyond current serological methods.
针对抗原呈递细胞(APC)的同种二聚体融合 DNA 疫苗针对独特型(Id)诱导多发性骨髓瘤(MM)小鼠模型中的强大肿瘤保护作用。为四名 MM 患者生成了类似的 Id 疫苗分子,主要有三个目标:(i)疫苗分子是否在小鼠中诱导真正的抗 Id 免疫反应?(ii)疫苗分子靶向 APC 是否增强免疫反应?(iii)接种疫苗的小鼠产生的抗 Id 抗体能否用于建立敏感的完全缓解(CR)测定,以便在患者接种疫苗之前?
针对四名 MM 患者的 Id 设计了针对小鼠主要组织相容性复合物(MHC)II 类分子的嵌合疫苗分子。
用针对患者 MHC 类 II 分子的嵌合疫苗对小鼠进行 DNA 疫苗接种,引发了针对患者骨髓瘤蛋白的特异性抗体。针对 MHC 类 II 的靶向大大增强了抗 Id 反应。小鼠抗 Id 抗体用于建立骨髓瘤蛋白特异性酶联免疫吸附测定(ELISA),比常规血清蛋白电泳和免疫固定法敏感 75 至 1500 倍。
这些结果为在 CR 患者中测试靶向 DNA Id 疫苗铺平了道路。可以建立针对 Id 和患者的特异性 ELISA,从而评估 CR 的深度超出当前的血清学方法。