Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma

Abstract

Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

“…One way of modification of MSCs is the possibility of releasing conditional replicative oncolytic viruses [50][51][52][53]. When oncolytic viruses are systemically delivered, the host immune system is responsible for the defense, which results in the elimination of the circulating viruses before they can reach the tumor site.…”

“…In a great number of experiments, adenoviruses and their modified versions (incorporation of different amino acid sections) were used as delivery vectors of viral load specific to the tumor site [50][51][52][53]103]. One of the difficulties in the treatment of conditions such as cancer is the need to deliver large quantities of the therapeutic agent for extended periods of time.…”

Anticancer Gene Transfer for Cancer Gene Therapy

“…Briefly, the immune system is by passed by viruses that are camouflaged under a different capsid or shielded with chemical compounds like polyethylene glycol in order to "trick" the immune system and be deliver to the tumor site. Stem cells, cancer stem cells, endothelial cells and progenitors, immune cells and even cancer cells as carriers have been, or are being tested for their efficacy and proof of principle (Iguchi et al, 2012;Hamada et al, 2007;Stoff-Khalili et al, 2007). Another approach to overcome the pre-existing immunity is the temporal immunosuppression using pharmacologic interference to bypass the adaptive and innate immune response.…”

Therapeutic potential of genetically modified mesenchymal stem cells

“…The payload of tumor homing MSC in cancer therapy was determined further in a study involving a conditionally replicating adenovirus vectors. 43 Improved transduction of adenoviral vectors to MSC has been shown using modification to include the RGD (Arg-Gly-Asp) motif on the penton fiber. Adopting this strategy, Kanehira et al 44 transduced NK4, an antagonist of hepatocyte growth factor and significantly prolonged the survival of mice bearing colon-26 cell line xenograft in lungs by inhibiting angiogenesis and lymphangiogenesis and inducing apoptosis of tumor cells.…”