Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Atherosclerosis. 2010 Feb;208(2):382-9. doi: 10.1016/j.atherosclerosis.2009.07.043. Epub 2009 Jul 30.
F16, F8 and L19 are three fully human monoclonal antibodies, specific to splice isoforms of tenascin-C and fibronectin, which stain sites of active tissue remodeling and which are currently in Phase I and II clinical trials as radio-immunoconjugates and immunocytokines in patients with cancer and arthritis. The characterization of atherosclerosis using these antibodies may open novel pharmacodelivery options for the imaging and treatment of cardiovascular conditions. It may also allow a better assessment of the corresponding immunoconjugates in polymorbid patients with atherosclerotic plaques.
We performed a comparative immunohistochemical analysis with the F16, F8 and L19 antibodies in 28 freshly frozen human carotid plaques and in 11 normal arteries. Furthermore, we assessed the localization of the antibodies in relation to the infiltrating macrophages, vasa vasorum and Ki67-positive proliferating cells of the plaque.
The F16 antibody, specific to the extra-domain A1 of tenascin-C, stained plaques with a selective and intense pattern, while F8 and L19, specific to the EDA and EDB domains of fibronectin, respectively, exhibited a less selective and intense staining. In immunofluorescence, F16 was found to bind regions rich in macrophages, vasa vasorum and proliferating cells, while showing no detectable vs. weak staining of normal arteries and of quiescent plaque structures.
The human monoclonal antibody F16 stains areas of active tissue remodeling in atherosclerotic plaques and may thus deserve to be investigated as a suitable building block for the development of radiopharmaceuticals for plaque imaging or for the antibody-based targeted delivery of therapeutic agents to atherosclerotic lesions.
F16、F8 和 L19 是三种完全人源化的单克隆抗体，特异性针对 tenascin-C 和纤维连接蛋白的剪接异构体，这些抗体可染色组织重塑的活跃部位，目前正在进行 I 期和 II 期临床试验，作为放射性免疫偶联物和免疫细胞因子，用于癌症和关节炎患者。使用这些抗体对动脉粥样硬化进行特征描述可能为心血管疾病的成像和治疗提供新的药物传递选择。它还可以允许在患有动脉粥样硬化斑块的多病态患者中更好地评估相应的免疫偶联物。
我们使用 F16、F8 和 L19 抗体在 28 个新鲜冷冻的人颈动脉斑块和 11 个正常动脉中进行了比较免疫组织化学分析。此外，我们评估了抗体在斑块中浸润的巨噬细胞、血管丛和 Ki67 阳性增殖细胞中的定位。
F16 抗体特异性针对 tenascin-C 的外显子 A1 区域，选择性和强烈地染色斑块，而 F8 和 L19 抗体分别特异性针对纤维连接蛋白的 EDA 和 EDB 结构域，显示出不那么选择性和强烈的染色。在免疫荧光中，发现 F16 结合富含巨噬细胞、血管丛和增殖细胞的区域，而对正常动脉和静止斑块结构几乎没有检测到或弱染色。
人源化单克隆抗体 F16 可染色动脉粥样硬化斑块中的活跃组织重塑区域，因此值得作为放射性药物开发的合适构建块进行研究，用于斑块成像或用于针对动脉粥样硬化病变的抗体靶向递送治疗剂。
