Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo

Abstract

Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor agents. Interferon-α (IFNα) has been used in clinic to treat various types of tumors; however, because of its short half-life, significant therapeutic effects require high doses that often results in serious side effects. Here, we tested whether MSCs continuingly secreting IFNα can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFNα. We found that even a small number of IFNα-secreting MSCs could potently halt B16 tumor growth in vivo. The antitumor activity of IFNα-secreting MSCs was largely abolished in immunodeficient mice, an effect largely attributed to natural killer cells and CD8(+) T cells. Therefore, IFNα-secreting MSCs provide an innovative strategy for tumor therapy.

Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells Producing IL15 Eradicate Established Pancreatic Tumor in Syngeneic Mice

“…In this study, there was an absence of high systemic level of IL15, suggesting that MSC-IL15 may be able to reduce undesired side effects. Moreover, we also did not observe intravenously administered MSC-IL15 homing in other tissues, which is consistent with previous reports (19,20). This property adds advantage toward using MSC to deliver IL15 in avoiding organ toxicity.…”

Type I interferons in anticancer immunity

“…An NK cell line genetically engineered to express human IFNα has improved cyto toxicity functions against HCC cells in vitro, as well as in xenograft tumour models 84 . Similarly, mesenchymal stem cells modified to express mouse IFNα potently halt the growth of B16 melanomas in vivo, an effect that was dependent on T cells and NK cells 85 . As an alter native approach, human myeloid cells overexpressing IFNβ have been created by transducing induced pluripotent stem cells (iPSCs) with an IFNβcoding lentivirus, followed by the induction of differentiation in vitro 86 .…”

Mesenchymal stem cells and infectious diseases: Smarter than drugs

“…It has been shown by several groups that MSCs can be utilized as carriers to deliver high levels of IFN-␣, [36] or chemotherapeutic prodrugs to tumors [37]. Similarly, it is possible to load MSCs with antibiotics.…”