Gene-cell therapy of cancer using a self-inactivating - retroviral vectors inducibly expressing tumour necrosis factor alpha in human mesenchymal stem cells.

Project leader: Silvia Tyčiaková
Project duration: 2009 - 2011

This project is a continuation of our previous long-standing work on improvements of retrovirus vectors for gene therapy and the use of the protein-cytokine Tumour Necrosis Factor alpha (TNFa), an apoptosis-inducing antitumour agent. Encouraged by these studies, we now intend to exploit mesenchymal stem cells (MSC), which are known for their ability to home in on tumours, and to develop the use of safer self-inactivating (SIN) vectors containing the TNFa gene. For this to be successful, the expression of TNFa needs to be inducibly controlled. Thus, we will construct a SIN vector containing TNFa under the control of the tet promoter that can be upregulated by the addition of the antibiotic, doxycycline. We will confirm the inducibility and biological effectiveness of this vector in vitro and then assess its ability to transduce isolated human MSC. The ability of transduced MSC to inducibly express TNFa and hence eliminate tumour cells in vivo will then be examined in human tumour xenograft experiments.