PMID- 17457213
OWN - NLM
STAT- MEDLINE
DCOM- 20070612
LR  - 20220309
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 30
IP  - 4
DP  - 2007 May-Jun
TI  - "Pathogen-mimicking" nanoparticles for vaccine delivery to dendritic cells.
PG  - 378-95
AB  - A clinically relevant delivery system that can efficiently target and deliver 
      antigens and adjuvant to dendritic cells (DCs) is under active investigation. 
      Immunization with antigens and immunomodulators encapsulated in 
      poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles elicits potent cellular 
      immune responses; but understanding how this mode of delivery affects DCs and 
      priming of naive T cells needs further investigation. In the current study, we 
      assessed the extent of maturation of DCs after treatment with monophosphoryl 
      lipid A (MPLA) encapsulated in PLGA nanoparticles and the generation of primary 
      T-cell immune responses elicited by DCs loaded with antigens using this approach. 
      Results indicated that DCs up-regulated the expression of surface maturation 
      markers and demonstrated an enhanced allostimulatory capacity after treatment 
      with MPLA containing PLGA nanoparticles. Treatment of DCs with MPLA containing 
      nanoparticles released high amounts of proinflammatory and TH1 (T helper 1) 
      polarizing cytokines and chemokines greater than that achieved by MPLA in 
      solution. The delivery of ovalbumin in PLGA nanoparticles to DCs induced potent 
      in vitro and in vivo antigen-specific primary TH1 immune responses that were 
      furthermore enhanced with codelivery of MPLA along with the antigen in the 
      nanoparticle formulation. Delivery of MUC1 lipopeptide (BLP25, a cancer vaccine 
      candidate) and MPLA in PLGA nanoparticles to human DCs induced proliferation of 
      MUC1 reactive T cells in vitro demonstrating the break in tolerance to 
      self-antigen MUC1. These results demonstrated that targeting antigens along with 
      toll-like receptor ligands in PLGA nanoparticles to DCs is a promising approach 
      for generating potent TH1 polarizing immune responses that can potentially 
      override self-tolerance mechanisms and become beneficial in the immunotherapy of 
      cancer and infectious diseases.
FAU - Elamanchili, Praveen
AU  - Elamanchili P
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, 3118, Dentistry/Pharmacy Centre, 
      University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.
FAU - Lutsiak, Christine M E
AU  - Lutsiak CM
FAU - Hamdy, Samar
AU  - Hamdy S
FAU - Diwan, Manish
AU  - Diwan M
FAU - Samuel, John
AU  - Samuel J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cancer Vaccines)
RN  - 0 (Lipid A)
RN  - 0 (Polymers)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - MWC0ET1L2P (monophosphoryl lipid A)
SB  - IM
MH  - Animals
MH  - Cancer Vaccines/*chemistry
MH  - Cell Proliferation
MH  - Dendritic Cells/*immunology/metabolism
MH  - *Drug Delivery Systems
MH  - Immunotherapy/*methods
MH  - Lactic Acid/chemistry
MH  - Lipid A/analogs & derivatives/chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/*chemistry
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/chemistry
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
MH  - Up-Regulation
EDAT- 2007/04/26 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/04/26 09:00
PHST- 2007/04/26 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/04/26 09:00 [entrez]
AID - 00002371-200705000-00003 [pii]
AID - 10.1097/CJI.0b013e31802cf3e3 [doi]
PST - ppublish
SO  - J Immunother. 2007 May-Jun;30(4):378-95. doi: 10.1097/CJI.0b013e31802cf3e3.