PMID- 12140735
OWN - NLM
STAT- MEDLINE
DCOM- 20020916
LR  - 20131121
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 9
IP  - 16
DP  - 2002 Aug
TI  - Biodegradable polymer-based interleukin-12 gene delivery: role of induced 
      cytokines, tumor infiltrating cells and nitric oxide in anti-tumor activity.
PG  - 1075-84
AB  - The objective of this study was to investigate the role of induced cytokines, 
      tumor infiltrating cells and nitric oxide (NO) in anti-tumor activity upon 
      intratumoral injection of free and condensed plasmid DNA encoding murine 
      interleukin-12 (pmIL-12) into BALB/c mice bearing subcutaneous tumors. 
      Poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA) was used for complex formation 
      with pmIL-12 in presence of 5% (w/v) glucose. Upon characterization, PAGA/pmIL-12 
      (3/1, +/-) complexes were found to be most effective in gene transfer and were 
      used consistently throughout this study. The levels of mIL-12 p70 and induced 
      cytokines were determined by ELISA in the supernatant of the cultured tumors of 
      the CT-26 subcutaneous tumor bearing BALB/c female mice 48 h after intratumoral 
      injection of PAGA/pmIL-12 complexes and naked pmIL-12. The levels of IL-12, 
      IFN-gamma, TNF-alpha and NO were higher for the PAGA/pmIL-12 complexes than those 
      for the naked pmIL-12, PAGA alone and 5% glucose injected groups. The relative 
      presence of natural killer (NK) cells, CD4(+) T cells, and antigen presenting 
      cells, such as macrophages and dendritic cells determined using 
      immunohistochemistry was higher for PAGA/pmIL-12 complexes compared with naked 
      pmIL-12. The presence of CMV promoter in plasmid encoding IL-12 cDNAs did not 
      induce any type I interferon response. There was a significant improvement in the 
      survival rate and the inhibition of tumor growth after repeated injections of 
      PAGA/pmIL-12 complexes.
FAU - Maheshwari, A
AU  - Maheshwari A
AD  - Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 
      84112-5820, USA.
FAU - Han, S
AU  - Han S
FAU - Mahato, R I
AU  - Mahato RI
FAU - Kim, S W
AU  - Kim SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Cytokines)
RN  - 0 (poly((4-aminobutyl)glycolic acid))
RN  - 187348-17-0 (Interleukin-12)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Adenocarcinoma/immunology/pathology/*therapy
MH  - Animals
MH  - Biodegradation, Environmental
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/immunology
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Interleukin-12/*genetics/immunology
MH  - Killer Cells, Natural/immunology
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - Macrophages
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Nitric Oxide/metabolism
MH  - Plasmids
MH  - Polyglycolic Acid/*analogs & derivatives
MH  - Survival Rate
MH  - Tumor Cells, Cultured
EDAT- 2002/07/26 10:00
MHDA- 2002/09/17 10:01
CRDT- 2002/07/26 10:00
PHST- 2001/02/21 00:00 [received]
PHST- 2001/12/20 00:00 [accepted]
PHST- 2002/07/26 10:00 [pubmed]
PHST- 2002/09/17 10:01 [medline]
PHST- 2002/07/26 10:00 [entrez]
AID - 10.1038/sj.gt.3301766 [doi]
PST - ppublish
SO  - Gene Ther. 2002 Aug;9(16):1075-84. doi: 10.1038/sj.gt.3301766.