Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

  • Commissione europea
  • CORDIS
  • Progetti e risultati
  • Obtention of receptor and/or transcriptionally targeted adenoviral vectors efficiently and specifically expressing a therapeutic gene in hepatoma, adenocarcinoma and glioblastoma cell lines
FP5

TARGETED GENE VECTOR Sintesi della relazione

Project ID: QLK3-CT-1999-00364
Finanziato nell'ambito di: FP5-LIFE QUALITY
Paese: Germany

Obtention of receptor and/or transcriptionally targeted adenoviral vectors efficiently and specifically expressing a therapeutic gene in hepatoma, adenocarcinoma and glioblastoma cell lines

A set of adenoviral vectors were designed and engineered such as to provide efficient and specific expression of a therapeutic gene in hepatoma, adenocarcinoma and glioblastoma cell lines, and neuronal and glial primary cell cultures. For this various HC-Ad vectors were engineered (described above), and different therapeutic genes were incorporated. These were either expressed from constitutive promoters (human CMV, murine CMV, elongation factor 1 alpha), or regulatable promoters.

Generation and characterisation of HC-Ad vector HC-Ad-RS45
- This vector expresses soluble Tie-2 under the control of the MCMV promoter and inhibits angiogenesis.
- Inhibition of angiopoietin function by this vector may help to inhibit tumour growth in cancer as an adjuvant treatment.

Generation and characterisation of HC-Ad vector HC-Ad-RS46
- This vector expresses the soluble PEX domain of MMP2 under the control of the MCMV promoter and is suitable to inhibit matrix metalloproteinases.
- Matrix metalloproteinase are crucially involved in the invasion and metastasis of tumour cells. The expression of the secreted PEX domain in hepatic cancer may inhibit tumour growth by inhibiting the activity of matrix metalloproteinases.
- Generation and characterisation of HC-Ad vector HC-Ad-RS24 and RS25
- These two vectors express the murine and the human, respectively, IL12 under the control of the inducible TTRB promoter.
- Using these vectors, it is possible to induce expression in hepatocytes by oral administration of low doses of mifepristone.

Generation and characterisation of HC-Ad vector HC-Ad-RS23
- This vector expresses the human VEGF Receptor 1 (s-FLT-1) under the control of the inducible TTRB promoter.
- VEGF is a critical factor for the generation of new vessels (neoangiogenesis) in tumours. This vector allows the local inhibition of VEGF by genetic modification of normal hepatocytes. Only upon oral administration of mifepristone is VEGF produced in normal hepatocytes, thereby locally preventing function of VEGF expressed from the tumour.

Generation of a PEDF expressing HC-Ad vector
- The vector was constructed to express the PEDF cDNA from the hCMV promoter. This molecule has anti-angiogenic properties.

Contatto

Stefan KOCHANEK, (Head, gene therapy laboratory)
Tel.: +49-73150033647
Fax: +49-73150033664
E-mail