PMID- 18654612
OWN - NLM
STAT- MEDLINE
DCOM- 20090113
LR  - 20211020
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 15
IP  - 12
DP  - 2008 Dec
TI  - IL-18-producing Salmonella inhibit tumor growth.
PG  - 787-94
LID - 10.1038/cgt.2008.48 [doi]
AB  - Previous studies have shown that intravenously applied bacteria can accumulate in 
      tumors and lead to sporadic tumor regression. Recently, systemic administration 
      of attenuated Salmonella typhimurium was demonstrated to generate no significant 
      side effects in humans, but also no antitumor responses. We report the enhanced 
      antitumor activity in preclinical mouse cancer models of nonvirulent S. 
      typhimurium engineered to synthesize the cytokine Interleukin-18 (IL-18). 
      IL-18-producing bacteria (but not control bacteria) inhibit the growth of primary 
      subcutaneous tumors as well as pulmonary metastases in immunocompetent mice 
      challenged with syngeneic multidrug-resistant clones of murine carcinoma cell 
      lines, without overt toxicity to normal tissues. Antitumor activity was 
      associated with increased accumulation of T-lymphocytes and NK cells in tumors, 
      and massive infiltration of granulocytes, as well as increased intra-tumoral 
      production of several cytokines. In summary, these findings provide evidence of 
      promising preclinical antitumor activity of IL-18-expressing, attenuated S. 
      typhimurium, suggesting a novel strategy for cancer immunotherapy.
FAU - Loeffler, M
AU  - Loeffler M
AD  - Burnham Institute for Medical Research, La Jolla, California 92037, USA.
FAU - Le'Negrate, G
AU  - Le'Negrate G
FAU - Krajewska, M
AU  - Krajewska M
FAU - Reed, J C
AU  - Reed JC
LA  - eng
GR  - P01 CA069381/CA/NCI NIH HHS/United States
GR  - P01 CA069381-020002/CA/NCI NIH HHS/United States
GR  - CA-69381/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080725
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Genetic Therapy
MH  - Genetic Vectors
MH  - Interleukin-18/*genetics/metabolism
MH  - Killer Cells, Natural/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Animal
MH  - Neoplasms/metabolism/*therapy
MH  - Protein Engineering
MH  - Salmonella/*genetics/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC2760299
MID - NIHMS138640
EDAT- 2008/07/26 09:00
MHDA- 2009/01/14 09:00
PMCR- 2009/10/12
CRDT- 2008/07/26 09:00
PHST- 2008/07/26 09:00 [pubmed]
PHST- 2009/01/14 09:00 [medline]
PHST- 2008/07/26 09:00 [entrez]
PHST- 2009/10/12 00:00 [pmc-release]
AID - cgt200848 [pii]
AID - 10.1038/cgt.2008.48 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2008 Dec;15(12):787-94. doi: 10.1038/cgt.2008.48. Epub 2008 Jul 
      25.