Encapsulation of proteins and peptides into biodegradable poly(D,L-lactide-co-glycolide) microspheres prolongs and enhances antigen presentation by human dendritic cells.
Dendritic cell (DC)-based immunotherapy has been hampered by the lack of suitable methods for antigen delivery. Here, we use biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA-MS) as carriers of peptides and proteins for antigen delivery to human monocyte-derived DC (MoDC). Compared to soluble proteins, MHC classes I and II-restricted presentation of PLGA-MS-encapsulated proteins and peptides by MoDC was markedly prolonged and proteins were presented 50-fold more efficiently on class I molecules. The vaccination of mice with DC loaded with PLGA-MS-encapsulated proteins raised strong and persisting cytotoxic T cell responses. In conclusion, antigen delivery via PLGA-MS markedly enhanced the duration of antigen presentation by human MoDC and the potency of DC-based vaccination.
Waeckerle-Men
Ying
Y
Research Department, Cantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland.
Allmen
Edith Uetz-von
EU
Gander
Bruno
B
Scandella
Elke
E
Schlosser
Eva
E
Schmidtke
Gunter
G
Merkle
Hans P
HP
Groettrup
Marcus
M
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003692:Delayed-Action Preparations; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D019344:Lactic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
D003692:Delayed-Action Preparations; D010446:Peptide Fragments; D010455:Peptides; D011108:Polymers; D011506:Proteins; D013745:Tetanus Toxoid; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid