Artificial exosomes as tools for basic and clinical immunology.
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.
The Anthony Nolan Research Institute, Royal Free Hospital, London, UK. medhugodoc@gmail.com
Hugo
H
De La Peña
J A
JA
Madrigal
Sylvie
S
Rusakiewicz
Martin
M
Bencsik
Gareth W V
GW
Cave
Ali
A
Selman
Robert C
RC
Rees
Paul J
PJ
Travers
Italo A
IA
Dodi
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D055354:Exosomes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D008081:Liposomes / Q000138:chemical synthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D008279:Magnetic Resonance Imaging; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods
D007140:Immunoglobulin Fab Fragments; D008081:Liposomes