Inhibition of murine K-BALB and CT26 tumour growth using a Semliki Forest virus vector with enhanced expression of IL-18.
The enhanced Semliki Forest virus vector (SFV10-E), an RNA-based suicide expression vector system, expresses foreign genes at levels up to 10x higher than the original SFV10 vector. This vector has been used previously to express interleukin-12 for a tumour treatment study in a BALB/c murine model. Interleukin-18, an IFN-gamma-inducing cytokine, plays a key role in the early induction of T helper1 (Th1) cell-mediated immune responses in addition to anti-angiogenic activity. In this study, the murine IL-18 gene along with an Ig-kappa leader sequence was cloned into the SFV10-E vector. The pSFV10-E-IL-18 construct was characterised in vitro for levels of expression and secretion, and the production of biologically active IL-18 was confirmed. An in vivo tumour treatment study using high titre rSFV10-E-IL-18 virus-like particles to treat subcutaneous K-BALB and CT26 tumours in BALB/c mice demonstrated therapeutic efficacy including the disappearance of tumour cells in a minority of treated animals. Tumour regression was associated with induction of avascular and suppurative necrosis.
Chikkanna-Gowda
C P
CP
Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland.
McNally
S
S
Sheahan
B J
BJ
Fleeton
M N
MN
Atkins
G J
GJ
D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D012672:Semliki forest virus / Q000235:genetics*
D020382:Interleukin-18; D007371:Interferon-gamma