PMID- 15625541
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20071114
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 11
IP  - 1
DP  - 2005 Jan
TI  - FLT3 ligand administration after hematopoietic cell transplantation increases 
      circulating dendritic cell precursors that can be activated by CpG 
      oligodeoxynucleotides to enhance T-cell and natural killer cell function.
PG  - 23-34
AB  - Dendritic cells (DCs) are key effectors in innate immunity and play critical 
      roles in triggering adaptive immune responses. FLT3 ligand (FLT3-L) is essential 
      for DC development from hematopoietic progenitors. In a phase I clinical trial, 
      we demonstrated that immunotherapy with subcutaneous injection of FLT3-L is safe 
      and well tolerated in cancer patients recovering from autologous hematopoietic 
      cell transplantation (HCT). FLT3-L administration significantly increased the 
      frequency and absolute number of blood DC precursors without affecting other 
      mature cell lineages during the 6-week course of FLT3-L therapy. After 14 days of 
      FLT3-L administration, the number of blood CD11c + DCs, plasmacytoid DCs (PDCs), 
      and CD14 + monocytes increased by 5.3-, 2.9-, 3.8-fold, respectively, and was 
      maintained at increased levels throughout FLT3-L therapy. FLT3-L-increased blood 
      DCs in HCT patients were immature and had modest enhancing effects on in vitro 
      T-cell proliferation to antigens and natural killer (NK) cell function. The 
      addition of type B CpG oligodeoxynucleotides (ODNs) to peripheral blood 
      mononuclear cells obtained from HCT patients receiving FLT3-L therapy induced 
      rapid maturation of both CD11c + DCs and PDCs and enhanced T-cell proliferative 
      responses. In addition, CpG ODN induced potent activation of NK cells from 
      FLT3-L-treated patients with increased surface CD69 expression and augmented 
      cytotoxicity. CpG ODN-induced activation of NK cells was primarily via an 
      indirect mechanism through PDCs. These findings suggest that FLT3-L mobilization 
      of DC precursors followed by a specific DC stimulus such as CpG ODN may provide a 
      novel strategy to manipulate antitumor immunity in patients after HCT.
FAU - Chen, Wei
AU  - Chen W
AD  - University of Minnesota Cancer Center, Minneapolis, Minnesota 5455, USA. 
      chenw@umn.edu
FAU - Chan, Anissa S H
AU  - Chan AS
FAU - Dawson, Amanda J
AU  - Dawson AJ
FAU - Liang, Xueqing
AU  - Liang X
FAU - Blazar, Bruce R
AU  - Blazar BR
FAU - Miller, Jeffrey S
AU  - Miller JS
LA  - eng
GR  - R01 CA72669/CA/NCI NIH HHS/United States
PT  - Clinical Trial
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, P.H.S.
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (Membrane Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (flt3 ligand protein)
SB  - IM
MH  - Adult
MH  - Antigen Presentation
MH  - Blood Cell Count
MH  - Breast Neoplasms/immunology/therapy
MH  - Cell Differentiation/drug effects
MH  - CpG Islands
MH  - Dendritic Cells/cytology/*drug effects/physiology
MH  - Female
MH  - Flow Cytometry
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Immunity/drug effects
MH  - Killer Cells, Natural/*drug effects/physiology
MH  - Lymphocyte Activation
MH  - Lymphoma/immunology/therapy
MH  - Male
MH  - Membrane Proteins/*administration & dosage/pharmacology
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides/*pharmacology
MH  - T-Lymphocytes/*drug effects/physiology
EDAT- 2004/12/31 09:00
MHDA- 2005/07/01 09:00
CRDT- 2004/12/31 09:00
PHST- 2004/12/31 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2004/12/31 09:00 [entrez]
AID - S1083879104005592 [pii]
AID - 10.1016/j.bbmt.2004.08.004 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2005 Jan;11(1):23-34. doi: 
      10.1016/j.bbmt.2004.08.004.