PMID- 15728471
OWN - NLM
STAT- MEDLINE
DCOM- 20050419
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 5
DP  - 2005 Mar 1
TI  - In vivo manipulation of dendritic cells overcomes tolerance to unmodified 
      tumor-associated self antigens and induces potent antitumor immunity.
PG  - 2645-52
AB  - Most tumor-associated Ags are self proteins that fail to elicit a T cell response 
      as a consequence of immune tolerance. Dendritic cells (DCs) generated ex vivo 
      have been used to break tolerance against such self Ags; however, in vitro 
      manipulation of DCs is cumbersome and difficult to control, resulting in vaccines 
      of variable potency. To address this problem we developed a method for loading 
      and activating DCs, in situ, by first directing sufficient numbers of DCs to 
      peripheral tissues using Flt3 ligand and then delivering a tumor-associated Ag 
      and oligonucleotide containing unmethylated CG motifs to these tissues. In this 
      study, we show in three different tumor models that this method can overcome 
      tolerance and induce effective antitumor immunity. Vaccination resulted in the 
      generation of CD8(+) T and NK cell effectors that mediated durable tumor 
      responses without attacking normal tissues. These findings demonstrate that 
      unmodified tumor-associated self Ags can be targeted to DCs in vivo to induce 
      potent systemic antitumor immunity.
FAU - Okano, Fumiyoshi
AU  - Okano F
AD  - Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 
      94304, USA.
FAU - Merad, Miriam
AU  - Merad M
FAU - Furumoto, Katsuyoshi
AU  - Furumoto K
FAU - Engleman, Edgar G
AU  - Engleman EG
LA  - eng
GR  - HL57443/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Autoantigens)
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Retroviridae Proteins, Oncogenic)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (flt3 ligand protein)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.18.- (tyrosinase-related protein-1)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/administration & dosage/*immunology
MH  - Autoantigens/administration & dosage/*immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Carcinoembryonic Antigen/administration & dosage/immunology
MH  - Cell Line, Tumor
MH  - Cell Movement/immunology
MH  - Cell Proliferation
MH  - Colonic Neoplasms/*immunology/pathology/*therapy
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Female
MH  - *Immune Tolerance
MH  - Killer Cells, Natural/immunology
MH  - Male
MH  - Melanoma, Experimental/*immunology/pathology/*therapy
MH  - Membrane Proteins/administration & dosage/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Oligodeoxyribonucleotides/administration & dosage/immunology
MH  - Oxidoreductases/administration & dosage/immunology
MH  - Retroviridae Proteins, Oncogenic/administration & dosage/immunology
MH  - Viral Envelope Proteins/administration & dosage/immunology
EDAT- 2005/02/25 09:00
MHDA- 2005/04/20 09:00
CRDT- 2005/02/25 09:00
PHST- 2005/02/25 09:00 [pubmed]
PHST- 2005/04/20 09:00 [medline]
PHST- 2005/02/25 09:00 [entrez]
AID - 174/5/2645 [pii]
AID - 10.4049/jimmunol.174.5.2645 [doi]
PST - ppublish
SO  - J Immunol. 2005 Mar 1;174(5):2645-52. doi: 10.4049/jimmunol.174.5.2645.