De La Peña Hugo, Madrigal J A, Rusakiewicz Sylvie, Bencsik Martin, Cave Gareth W V, Selman Ali, Rees Robert C, Travers Paul J, Dodi Italo A
The Anthony Nolan Research Institute, Royal Free Hospital, London, UK.
J Immunol Methods. 2009 May 31;344(2):121-32. doi: 10.1016/j.jim.2009.03.011. Epub 2009 Apr 1.
Dendritic cell derived exosomes are able to mediate and modulate immune responses in vivo by semi-direct T cell activation. T cells can eradicate primary, metastatic, relapsed tumours and ameliorate otherwise fatal viral infections. Not surprisingly activation and expansion of T cells has become one of the main focuses for immunotherapy. Using nanotechnology, we have developed targeted and traceable in vivo artificial exosomes by coating liposomes (FDA approved) with an optimized number of MHC Class I/peptide complexes and a selected specific range of ligands for adhesion, early activation, late activation and survival T cell receptors. These targeted artificial exosomes are traceable both in vitro and in vivo via fluorescent and Magnetic Resonance Imaging and facilitate imaging of specific areas by applying localised nuclear magnetic interactions of hydrogens via super paramagnetic labels. Here we show that artificial exosomes activate and expand functional antigen specific T cells at sufficient levels. This novel system has potential basic and clinical applications in immunology where the study of membrane interactions is desired.
树突状细胞衍生的外泌体能够通过半直接激活T细胞在体内介导和调节免疫反应。T细胞可以根除原发性、转移性、复发性肿瘤,并改善其他致命的病毒感染。毫不奇怪,T细胞的激活和扩增已成为免疫治疗的主要重点之一。利用纳米技术,我们通过用优化数量的MHC I类/肽复合物和选定的特定范围的配体(用于粘附、早期激活、晚期激活和存活T细胞受体)包被脂质体(FDA批准),开发了靶向且可追踪的体内人工外泌体。这些靶向人工外泌体在体外和体内均可通过荧光和磁共振成像进行追踪,并通过超顺磁性标记应用氢的局部核磁相互作用来促进特定区域的成像。在这里,我们表明人工外泌体能够充分激活和扩增功能性抗原特异性T细胞。这个新系统在需要研究膜相互作用的免疫学领域具有潜在的基础和临床应用价值。