Mesenchymal stem cell directed baculoviral gene therapy of colon cancer.

e14573 Background: Insufficient targeting of the therapeutic genes to tumor cells is one of the major reasons of failure in cancer gene therapy. Mesenchymal stem cells (MSC) can easily home to the tumor sites when administered intravenously because of the chronic inflammatory process induced by the tumor cells. Methods: In the current study, we constructed baculoviral vectors (BVs) carrying cytosine deaminase (CD) (BV-CD) or green fluorescence protein genes and tested the transduction efficiency of the vectors and in vivo efficacy of the bone marrow derived MSC (BM-MSC) loaded with BV-CD vector in a colon cancer model in BALB/c mice. Three groups of mice with 6 mice in each having approximately 50 mm3 of tumor nodules established by subcutaneous injection of CRL2638 colon cancer cells were used. The control group was given iv PBS, the second group iv injection of 1×105 BM-MSCs and the third group iv injection of 1×105 BM-MSCs loaded with 100 MOI of BV-CD. All the mice were given ip 500 mg/kg 5-FC in 0.5 ml of volume for 10 days. Results: While the transduction efficiency of the recombinant baculoviral vectors was almost 100% in Sf-9 insect cells at the dose of 100 MOI, it was approximately 70% in mouse tumor cells and BM-MSCs of the BALB/c mice. The BV-CD treatment caused a significant in vitro cytotoxicity when used with 5-fluorocytosine in various tumor cells. No toxicity was observed when the vector used alone in mammalian cells. The recombinant vector loaded BM-MSCs caused a significant delay in tumor growth (p < 0.01) and increased the median survival time of the tumor bearing mice approximately 40% when compared to either controls or unloaded MSCs (p < 0.05). Conclusions: Our results show that the recombinant BV-CD vector could be used either alone or loaded into BM-MSCs, in the treatment of colorectal cancer.