Project

Prevention of peritoneal metastases by selective capture and killing of cancer cells by activated free microparticles and Lutetium-177 labeled nanobodies

Duration
01 October 2009 → 26 February 2015
Funding
Regional and community funding: IWT/VLAIO
Promotor
Research disciplines
  • Medical and health sciences
    • Morphological sciences
    • Oncology
    • Morphological sciences
    • Oncology
    • Morphological sciences
    • Oncology
Keywords
peritoneal metastases
 
Project description

Peritoneal metastases are, inter alia, for in ovarian and colorectal carcinoma patients, in, respectively, 75% and 13% of the cases and show a poor 5-year survival. Metastasis formation starts with the detachment of cancer cells from the primary tumor. The tumor environment promotes adhesion of these cancer cells. Activated fibroblasts (CAFS; cancer-associated fibroblasts) play an important role in the production of pro-adhesive extracellular matrix proteins (collagen type I, Tenascin C, ...). To prevent the formation of peritoneal metastases, we have developed a biological trap. For this purpose, cells were CAF in microparticles (500 - 700ùm) encapsulated. In vitro, ex vivo and in vivo experiments demonstrate that free cancer cells preferentially bind to CAF containing microparticles, and this also in the peritoneum of laboratory animals. The microparticles, after binding of free cancer cells, remove back we see a better overleveing ​​of mice. However, the technique does not allow to remove all microparticles. After therefore must catch the cancer cells to be slain in situ. During this project we want to investigate or radioisotope-tagged nanobodies towards the captured cancer cells or to the microparticle wall itself, the prisoner can kill cancer cells in situ. In this way the formation of peritoneal metastases could be prevented with minimal toxicity to the patient