PMID- 11929774
OWN - NLM
STAT- MEDLINE
DCOM- 20020617
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 8
DP  - 2002 Apr 15
TI  - Flt3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based 
      vaccines in patients with HER-2/neu-overexpressing cancers.
PG  - 2845-50
AB  - Dendritic cells (DCs) are potent antigen-presenting cells and have shown promise 
      to function as "natural" vaccine adjuvants. Currently, most cancer vaccine trials 
      using DCs generate autologous DCs ex vivo for each patient. Systemic treatment 
      with Flt3 ligand (FL) results in a marked increase of DCs in tissues such as 
      spleen and lymph nodes in mice and in the peripheral blood and skin of humans. In 
      light of these observations, we questioned whether FL could be used systemically 
      as a vaccine adjuvant to stimulate DC mobilization in vivo, circumventing the 
      need to generate DCs ex vivo. Ten patients with HER-2/neu-overexpressing cancer 
      were enrolled in a phase 1 study to receive a HER-2/neu peptide-based vaccine 
      targeting the intracellular domain of the HER-2/neu protein. All patients 
      received 20 microg/kg FL per day subcutaneously for 14 days. Five patients 
      received the HER-2/neu peptide-based vaccine alone on day 7 of the 14-day cycle, 
      and 5 patients received the vaccine admixed with 150 microg granulocyte 
      macrophage-colony-stimulating factor (GM-CSF) on day 7 of the FL cycle. T-cell 
      proliferative responses to HER-2/neu peptides and intracellular domain protein 
      suggest that vaccine regimens including FL as an adjuvant were not effective in 
      eliciting a significant HER-2/neu protein-specific T-cell proliferative response. 
      However, including FL as a vaccine adjuvant was effective in boosting the 
      precursor frequency of interferon-gamma-secreting HER-2/neu-specific T cells. The 
      small sample size of each group, however, did not allow a statistically 
      significant comparison of immune responses between the FL alone and FL with 
      GM-CSF arms. Finally, vaccine regimens including FL as a vaccine adjuvant were 
      associated with the development of apparent autoimmune phenomena in some 
      patients.
FAU - Disis, Mary L
AU  - Disis ML
AD  - Division of Oncology, University of Washington, Seattle, WA 98195-6527, USA. 
      ndisis@u.washington.edu
FAU - Rinn, Kristine
AU  - Rinn K
FAU - Knutson, Keith L
AU  - Knutson KL
FAU - Davis, Donna
AU  - Davis D
FAU - Caron, Dania
AU  - Caron D
FAU - dela Rosa, Corazon
AU  - dela Rosa C
FAU - Schiffman, Kathy
AU  - Schiffman K
LA  - eng
GR  - K08 CA61834/CA/NCI NIH HHS/United States
GR  - M01-RR00037/RR/NCRR NIH HHS/United States
GR  - R01 CA75163/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (flt3 ligand protein)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/pharmacology/therapeutic use
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & 
      dosage/immunology/pharmacology
MH  - Autoimmune Diseases/chemically induced
MH  - Breast Neoplasms/complications/metabolism/therapy
MH  - Cancer Vaccines/administration & dosage/*pharmacology
MH  - Dendritic Cells/cytology/drug effects
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/administration & 
      dosage/pharmacology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Membrane Proteins/*administration & dosage/immunology/pharmacology
MH  - Middle Aged
MH  - Ovarian Neoplasms/complications/metabolism/therapy
MH  - Peptide Fragments/administration & dosage/immunology/pharmacology
MH  - Receptor, ErbB-2/*administration & dosage/immunology/metabolism
MH  - T-Lymphocytes/drug effects/immunology/metabolism
EDAT- 2002/04/04 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/04/04 10:00
PHST- 2002/04/04 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/04/04 10:00 [entrez]
AID - S0006-4971(20)37971-4 [pii]
AID - 10.1182/blood.v99.8.2845 [doi]
PST - ppublish
SO  - Blood. 2002 Apr 15;99(8):2845-50. doi: 10.1182/blood.v99.8.2845.