Exosome Display technology: applications to the development of new diagnostics and therapeutics.
Exosome Display is a novel methodology enabling the manipulation of exosome protein content. This technology stems from the identification of addressing domains that mediate the specific distribution of proteins on exosomes. More particularly, Lactadherin expressed in non-mammary gland tissue has been found to localize to exosomes via binding of its C1C2 domain to exosome lipids. Exosome Display of soluble antigens and extracellular domains of membrane proteins that are not naturally found on exosomes occurs upon fusion of proteins with the Lactadherin C1C2 domain. Exosome Display of native full-length membrane proteins can also be achieved by non-restricted expression or sampling of membrane proteins on exosomes. These novel findings enable us to manipulate exosome composition and tailor exosomes with new desirable properties. The Exosome Display technology is very versatile since soluble, membrane-bound, trans-membrane or multimeric antigens that are not naturally found on exosomes can now be efficiently expressed at their surface in a native conformation. The technology was applied to the generation of antibodies against tumor biomarkers such as HLA/peptide complex. This antibody method called ExoMAb can be used to generate antibodies against any drug target candidates, notably including G-protein coupled receptors. The potential of Exosome Display technology for developing a broad range of novel diagnostics and therapeutics is discussed.
Delcayre
Alain
A
Anosys Inc. 1014 Menlo Park, CA 94025, USA. adelcayre@exothera.com
Estelles
Angeles
A
Sperinde
Jeffrey
J
Roulon
Thibaut
T
Paz
Pedro
P
Aguilar
Barbara
B
Villanueva
Janeth
J
Khine
SuSu
S
Le Pecq
Jean-Bernard
JB
D000906:Antibodies / Q000627:therapeutic use; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002460:Cell Line; D011992:Endosomes / Q000737:chemistry*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008894:Milk Proteins / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy; D019151:Peptide Library; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000906:Antibodies; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006680:HLA Antigens; C098942:MFGE8 protein, human; D008565:Membrane Proteins; D008894:Milk Proteins; D019151:Peptide Library; D011993:Recombinant Fusion Proteins