Scancell Limited, Department of Clinical Oncology, University of Nottingham, Nottingham, UK.
MAbs. 2009 Jan-Feb;1(1):71-85. doi: 10.4161/mabs.1.1.7492.
Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.
抗原/抗体复合物可以有效地将抗原呈递细胞靶向，从而刺激细胞免疫反应。由于制造困难和固有不稳定性，复合物已被证明是低效的癌症疫苗。然而，模拟抗原的抗独特型抗体已被证明可刺激抗体和 T 细胞反应。后者是由于在抗体的互补决定区 (CDR) 内表达的 T 细胞模拟表位，这些表位在体内可有效地递呈给树突状细胞。基于这一观察结果，我们设计了一种名为 ImmunoBody 的 DNA 疫苗平台，其中细胞毒性 T 淋巴细胞 (CTL) 和辅助 T 细胞表位取代了人 IgG1 抗体框架内的 CDR 区域。ImmunoBody 表达系统具有许多设计特点，可以快速生产广泛的疫苗。重链和轻链的 CDR 区域经过工程改造，包含独特的限制性内切酶位点，这些位点可以轻松打开，并插入编码 T 细胞表位的寡核苷酸。ImmunoBody 的可变区和恒定区也被限制性位点包围，允许轻松交换其他 IgG 亚型。在这里，我们展示了一系列 T 细胞表位可以插入到 ImmunoBody 载体中，并且在免疫接种后，这些 T 细胞表位可以有效地被加工和呈递，以刺激具有抗肿瘤活性的高频率辅助和 CTL 反应。
