PMID- 12384548
OWN - NLM
STAT- MEDLINE
DCOM- 20021129
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 62
IP  - 20
DP  - 2002 Oct 15
TI  - Interleukin 18 gene transfer expands the repertoire of antitumor Th1-type 
      immunity elicited by dendritic cell-based vaccines in association with enhanced 
      therapeutic efficacy.
PG  - 5853-8
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that can prime and 
      boost systemic antitumor immunity. Here, we have evaluated the ability of DCs 
      transfected to secrete the potent Th1-biasing cytokine interleukin (IL)-18 to 
      promote enhanced antitumor immunity in a mouse sarcoma model. DCs infected with a 
      recombinant adenovirus encoding IL-18 (AdIL18DC) expressed higher levels of MHC 
      and costimulatory molecules and were better stimulators than control DCs in mixed 
      leukocyte reactions in vitro. Immunization of BALB/c mice bearing established day 
      7 CMS4 tumors with tumor peptide-pulsed control Adpsi5-transfected DCs or 
      nontransduced DCs significantly inhibited the growth of established tumors but 
      did not lead to complete regression of established tumors. Importantly, 
      immunization with antigen-loaded AdIL18DC resulted in tumor rejection or further 
      suppression of tumor growth when compared with controls. The repertoire of 
      naturally presented tumor peptides recognized by splenocytes (as deduced in 
      IFN-gamma ELISA assays) from AdIL18DC-treated animals was far more diverse and of 
      greater magnitude than that of all other groups, in association with improved 
      therapeutic outcome. These results support the ability of IL-18 gene transfer to 
      enhance the capacity of DCs to drive broadly reactive Th1-type therapeutic 
      immunity prompted by single peptide epitope-based vaccines (i.e., epitope 
      spreading).
FAU - Tatsumi, Tomohide
AU  - Tatsumi T
AD  - Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 
      15261, USA.
FAU - Gambotto, Andrea
AU  - Gambotto A
FAU - Robbins, Paul D
AU  - Robbins PD
FAU - Storkus, Walter J
AU  - Storkus WJ
LA  - eng
GR  - CA 63350/CA/NCI NIH HHS/United States
GR  - CA 68067/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cancer Vaccines)
RN  - 0 (Interleukin-18)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cancer Vaccines/genetics/*immunology/therapeutic use
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/metabolism/physiology
MH  - Female
MH  - Gene Transfer Techniques
MH  - Immunotherapy, Adoptive/*methods
MH  - Interferon-gamma/biosynthesis/immunology
MH  - Interleukin-18/*genetics/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Sarcoma, Experimental/immunology/therapy
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Th1 Cells/*immunology
EDAT- 2002/10/18 04:00
MHDA- 2002/11/30 04:00
CRDT- 2002/10/18 04:00
PHST- 2002/10/18 04:00 [pubmed]
PHST- 2002/11/30 04:00 [medline]
PHST- 2002/10/18 04:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2002 Oct 15;62(20):5853-8.