Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro.
Biodegradable microspheres (MS) consisting of poly(D,L-lactide-co-glycolide) (PLGA) represent a promising alternative to conventional adjuvants. The adjustable pulsatile release of encapsulated material from such MS offers the potential to mimic the priming and boosting injections of conventional immunization regimens. In this paper, we demonstrate that MS can serve as antigen reservoirs in antigen presenting cells (APC), so that antigen is presented for extended periods of time (up to 9 days). In particular, we could show by measurement of IFN-gamma production that encapsulated peptides were presented to cytotoxic T lymphocytes (CTL) by mouse and human macrophages as well as by human dendritic cells in vitro for a longer time period as compared to soluble peptides. The extended antigen presentation may thus improve the CTL response in vivo. These results may be of paramount importance in cancer vaccination therapy since MS may serve as antigen reservoirs to extend the presentation time by APC used to boost the patient's immune response to tumor antigens.
Audran
Régine
R
Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Peter
Katrin
K
Dannull
Jens
J
Men
Ying
Y
Scandella
Elke
E
Groettrup
Marcus
M
Gander
Bruno
B
Corradin
Giampietro
G
D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004339:Drug Compounding; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008863:Microspheres; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D000953:Antigens, Protozoan; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D011108:Polymers; D015800:Protozoan Proteins; C105341:Ser-Tyr-Ile-Pro-Ser-Ala-Glu-Lys-Ile protein, Plasmodium; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; C041595:circumsporozoite protein, Protozoan; C448634:influenza matrix peptide (58-66); C478241:tyrosyl-leucyl-asparagyl-lysyl-isoleucyl-glutaminyl-asparagyl-seryl-leucine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma