Pereira Cândida F, Torensma Ruurd, Hebeda Konnie, Kretz-Rommel Anke, Faas Susan J, Figdor Carl G, Adema Gosse J
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Immunother. 2007 Oct;30(7):705-14. doi: 10.1097/CJI.0b013e31812e6256.
In vivo targeting of antigen-presenting cells (APCs) with antigens coupled to antibodies directed against APC-specific endocytic receptors is a simple and a promising approach to induce or modulate immune responses against those antigens. In a recent in vitro study, we have shown that targeting of APCs with an antigen coupled to an antibody directed against the endocytic receptor DC-SIGN effectively induces a specific immune response against that antigen. The aim of the present study was to determine the ability of the murine antihuman DC-SIGN antibody AZN-D1 to target APCs in a cynomolgus macaque model after its administration in vivo. Immunohistochemical analysis demonstrated that macaques injected intravenously with AZN-D1 have AZN-D1-targeted APCs in all lymph nodes (LNs) tested and in the liver. DC-SIGN-positive cells were mainly located in the medullary sinuses of the LNs and in the hepatic sinusoids in the liver. No unlabeled DC-SIGN molecules were found in the LN of AZN-D1-injected macaques. Morphologic criteria and staining of sequential LN sections with a panel of antibodies indicated that the DC-SIGN-targeted cells belong to the myeloid lineage of APCs. In conclusion, this is the first study that shows specific targeting of APCs in vivo by using antibodies directed against DC-SIGN.
用与针对抗原呈递细胞（APC）特异性内吞受体的抗体偶联的抗原在体内靶向APC，是诱导或调节针对这些抗原的免疫反应的一种简单且有前景的方法。在最近的一项体外研究中，我们已经表明，用与针对内吞受体DC-SIGN的抗体偶联的抗原靶向APC可有效诱导针对该抗原的特异性免疫反应。本研究的目的是确定鼠抗人DC-SIGN抗体AZN-D1在体内给药后在食蟹猴模型中靶向APC的能力。免疫组织化学分析表明，静脉注射AZN-D1的猕猴在所有测试的淋巴结（LN）和肝脏中都有AZN-D1靶向的APC。DC-SIGN阳性细胞主要位于LN的髓窦和肝脏的肝血窦中。在注射AZN-D1的猕猴的LN中未发现未标记的DC-SIGN分子。形态学标准和用一组抗体对连续LN切片进行染色表明，DC-SIGN靶向的细胞属于APC的髓系谱系。总之，这是第一项表明使用针对DC-SIGN的抗体在体内特异性靶向APC的研究。
