PMID- 17974997
OWN - NLM
STAT- MEDLINE
DCOM- 20071127
LR  - 20220408
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 21
DP  - 2007 Nov 1
TI  - Enhanced activation of human dendritic cells by inducible CD40 and Toll-like 
      receptor-4 ligation.
PG  - 10528-37
AB  - Despite the potency of dendritic cells (DC) as antigen-presenting cells for 
      priming adaptive immunity, DC-based cancer vaccines have been largely 
      insufficient to effectively reduce tumor burden or prevent tumor progression in 
      most patients. To enhance DC-based vaccines, we used the combination of a 
      synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 
      (TLR-4) ligation in human monocyte-derived DCs. The iCD40 receptor permits 
      targeted, reversible activation of CD40 in vivo, potentially bypassing the 
      essential role of CD4(+) T cells for activation of DCs. As a rigorous preclinical 
      study of this approach, we evaluated key parameters of DC activation and 
      function. Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of 
      interleukin (IL)-12p70 and IL-6, using iCD40 in combination with 
      lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic 
      production of both. Furthermore, this approach led to high expression of DC 
      maturation markers, epitope-specific CTL and T helper 1 responses, as well as DC 
      migration in vitro and in vivo. Moreover, use of iCD40-modified and 
      LPS-stimulated DCs led to targeted expansion of autologous T cells against 
      tumor-associated antigens, including prostate-specific membrane antigen, and 
      elimination of preestablished tumors, supporting this technology as a potent 
      strategy for DC-based cancer immunotherapy.
FAU - Lapteva, Natalia
AU  - Lapteva N
AD  - Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.
FAU - Seethammagari, Mamatha R
AU  - Seethammagari MR
FAU - Hanks, Brent A
AU  - Hanks BA
FAU - Jiang, Jianghong
AU  - Jiang J
FAU - Levitt, Jonathan M
AU  - Levitt JM
FAU - Slawin, Kevin M
AU  - Slawin KM
FAU - Spencer, David M
AU  - Spencer DM
LA  - eng
GR  - R01-CA120411/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Surface)
RN  - 0 (CCR7 protein, human)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, CCR7)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 3.4.17.21 (FOLH1 protein, human)
RN  - EC 3.4.17.21 (Glutamate Carboxypeptidase II)
SB  - IM
MH  - Animals
MH  - Antigens, Surface/immunology
MH  - CD40 Antigens/*physiology
MH  - Cancer Vaccines/immunology
MH  - Cell Line, Tumor
MH  - Cell Polarity
MH  - Dendritic Cells/*immunology
MH  - Glutamate Carboxypeptidase II/immunology
MH  - Humans
MH  - Interleukin-12/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, CCR7/analysis
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Th1 Cells/physiology
MH  - Toll-Like Receptor 4/*physiology
EDAT- 2007/11/03 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/11/03 09:00
PHST- 2007/11/03 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/11/03 09:00 [entrez]
AID - 67/21/10528 [pii]
AID - 10.1158/0008-5472.CAN-07-0833 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Nov 1;67(21):10528-37. doi: 10.1158/0008-5472.CAN-07-0833.