PMID- 15384929
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20210103
IS  - 1424-9634 (Electronic)
IS  - 1424-9634 (Linking)
VI  - 4
DP  - 2004 Sep 23
TI  - The impact of imiquimod, a Toll-like receptor-7 ligand (TLR7L), on the 
      immunogenicity of melanoma peptide vaccination with adjuvant Flt3 ligand.
PG  - 9
AB  - Dendritic cells (DCs) show promise as adjuvants in anticancer immunotherapeutic 
      strategies. Flt3 ligand (FL) is a hematopoietic growth factor that increases the 
      number of immature DCs in the blood and other tissues. We treated 27 patients 
      with metastatic or high-risk resected melanoma with s.c. FL daily for 14 d in 
      three 28 d cycles. Eighteen of these patients also received vaccination with 
      influenza (Flu), Melan-A (Mel), tyrosinase (Tyr), and NY-ESO-1 peptides. To 
      induce local DC maturation, 8 of the vaccinated patients had imiquimod, a 
      Toll-like receptor-7 ligand (TLR7L), applied topically to their vaccine sites. 
      Patients were monitored for clinical and hematological effects. Immune responses 
      were assessed by cutaneous reactivity to vaccination and by the induction of 
      peptide-specific CD8+ T-cells. Eight patients did not complete the protocol due 
      to adverse events related to their cancer. The treatment was generally safe and 
      well tolerated, although some patients developed clinically significant 
      toxicities related to FL. FL induced increases in immature CD11c+ and CD123+ 
      peripheral blood (PB) DCs. Other hematological effects included monocytosis, 
      granulocytosis, and thrombocytosis, which were marked in some patients. Cutaneous 
      reactions to peptide vaccination and circulating peptide-specific CD8+ T-cells 
      were more frequent in imiquimod-treated patients. FL treatment of melanoma 
      patients has pleiotropic clinical and hematological effects. In vivo maturation 
      of FL-generated DCs using imiquimod may increase immune responses to tumor 
      antigens.
FAU - Shackleton, Mark
AU  - Shackleton M
AD  - Cancer Vaccine Laboratory, Ludwig Institute for Cancer Research, Austin Health, 
      Studley Road, Heidelberg, 3084, Australia.
FAU - Davis, Ian D
AU  - Davis ID
FAU - Hopkins, Wendie
AU  - Hopkins W
FAU - Jackson, Heather
AU  - Jackson H
FAU - Dimopoulos, Nektaria
AU  - Dimopoulos N
FAU - Tai, Tsin
AU  - Tai T
FAU - Chen, Qiyuan
AU  - Chen Q
FAU - Parente, Phillip
AU  - Parente P
FAU - Jefford, Michael
AU  - Jefford M
FAU - Masterman, Kelly-Anne
AU  - Masterman KA
FAU - Caron, Dania
AU  - Caron D
FAU - Chen, Weisan
AU  - Chen W
FAU - Maraskovsky, Eugene
AU  - Maraskovsky E
FAU - Cebon, Jonathan
AU  - Cebon J
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040923
PL  - United States
TA  - Cancer Immun
JT  - Cancer immunity
JID - 101119871
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Aminoquinolines)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CTAG1B protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (flt3 ligand protein)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage/adverse effects
MH  - Adult
MH  - Aged
MH  - Aminoquinolines/*administration & dosage/adverse effects/immunology
MH  - Antigens, Neoplasm/immunology
MH  - Antineoplastic Agents/administration & dosage/adverse effects
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*administration & dosage/adverse effects/immunology
MH  - Cytokines/blood/immunology
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Humans
MH  - Imiquimod
MH  - Immunotherapy, Active/*methods
MH  - MART-1 Antigen
MH  - Male
MH  - Melanoma/*immunology/*therapy
MH  - Membrane Proteins/*administration & dosage/adverse effects/immunology
MH  - Middle Aged
MH  - Monophenol Monooxygenase/immunology
MH  - Neoplasm Proteins/immunology
MH  - Peptide Fragments/administration & dosage/adverse effects/*immunology
EDAT- 2004/09/24 05:00
MHDA- 2005/03/04 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/07/06 00:00 [received]
PHST- 2004/07/29 00:00 [accepted]
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - 040710 [pii]
PST - epublish
SO  - Cancer Immun. 2004 Sep 23;4:9.