PMID- 15205352
OWN - NLM
STAT- MEDLINE
DCOM- 20040806
LR  - 20210102
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 12
DP  - 2004 Jun 15
TI  - Targeting dendritic cells with antigen-containing liposomes: a highly effective 
      procedure for induction of antitumor immunity and for tumor immunotherapy.
PG  - 4357-65
AB  - Dendritic cells (DCs) are potent stimulators of immunity, and DCs pulsed with 
      tumor antigen ex vivo have applications in tumor immunotherapy. However, DCs are 
      a small population of cells, and their isolation and pulsing with antigen can be 
      impractical. Here we show that a crude preparation of plasma membrane vesicles 
      (PMV) from the highly metastatic murine melanoma (B16-OVA) and a surrogate tumor 
      antigen (OVA) can be targeted directly to DCs in vivo to elicit functional 
      effects. A novel metal-chelating lipid, 3(nitrilotriacetic 
      acid)-ditetradecylamine, was incorporated into B16-OVA-derived PMV, allowing 
      recombinant hexahistidine-tagged forms of single chain antibody fragments to the 
      DC surface molecules CD11c and DEC-205, to be conveniently "engrafted" onto the 
      vesicle surface by metal-chelating linkage. The modified PMV, or similarly 
      engrafted synthetic stealth liposomes containing OVA or OVA peptide antigen, were 
      found to target DCs in vitro and in vivo, in experiments using flow cytometry and 
      fluorescence confocal microscopy. When used as vaccines in syngeneic mice, the 
      preparations stimulated strong B16-OVA-specific CTL responses in splenic T cells 
      and a marked protection against tumor growth. Protection was dependent on the 
      simultaneous delivery of both antigen and a DC maturation or "danger signal" 
      signal (IFN-gamma or lipopolysaccharide). Administration of the DC-targeting 
      vaccine to mice challenged with B16-OVA cells induced a dramatic 
      immunotherapeutic effect and prolonged disease-free survival. The results show 
      that the targeting of antigen to DCs in this way is highly effective at inducing 
      immunity and protection against the tumor, with protection being at least 
      partially dependent on the eosinophil chemokine eotaxin.
FAU - van Broekhoven, Christina L
AU  - van Broekhoven CL
AD  - School of Biochemistry and Molecular Biology, Faculty of Science, John Curtin 
      School of Medical Research, The Australian National University, Canberra, 
      Australian Capital Territory, Australia.
FAU - Parish, Christopher R
AU  - Parish CR
FAU - Demangel, Caroline
AU  - Demangel C
FAU - Britton, Warwick J
AU  - Britton WJ
FAU - Altin, Joseph G
AU  - Altin JG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Amines)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Immunoglobulin Fragments)
RN  - 0 (Liposomes)
RN  - 0 (nitrilotriacetic acid ditetradecylamine)
RN  - 9006-59-1 (Ovalbumin)
RN  - KA90006V9D (Nitrilotriacetic Acid)
SB  - IM
MH  - Amines/administration & dosage/chemistry
MH  - Animals
MH  - Antigens, Neoplasm/*administration & dosage/*immunology
MH  - Dendritic Cells/*drug effects/*immunology
MH  - Female
MH  - Immunoglobulin Fragments/administration & dosage/chemistry
MH  - Immunotherapy/*methods
MH  - Liposomes
MH  - Male
MH  - Melanoma, Experimental/*immunology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitrilotriacetic Acid/administration & dosage/*analogs & derivatives/chemistry
MH  - Ovalbumin/immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2004/06/19 05:00
MHDA- 2004/08/07 05:00
CRDT- 2004/06/19 05:00
PHST- 2004/06/19 05:00 [pubmed]
PHST- 2004/08/07 05:00 [medline]
PHST- 2004/06/19 05:00 [entrez]
AID - 64/12/4357 [pii]
AID - 10.1158/0008-5472.CAN-04-0138 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Jun 15;64(12):4357-65. doi: 10.1158/0008-5472.CAN-04-0138.