Mesenchymal stem cell carriers enhance anti-tumor efficacy of oncolytic virotherapy

Abstract

Oncolytic viruses (OVs) specifically infect, replicate and eventually destroy tumor cells, with no concomitant toxicity to adjacent normal cells. Furthermore, OVs can regulate tumor microenvironments and stimulate anti-tumor immune responses. Mesenchymal stem cells (MSCs) have inherent tumor tropisms and immunosuppressive functions. MSCs carrying OVs not only protect viruses from clearing by the immune system, but they also deliver the virus to tumor lesions. Equally, cytokines released by MSCs enhance anti-tumor immune responses, suggesting that MSCs carrying OVs may be considered as a promising strategy in enhancing the anti-tumor efficacies of virotherapy. In the present review, preclinical and clinical studies were evaluated and discussed, as well as the effectiveness of MSCs carrying OVs for tumor treatment.

Keywords: cellular carriers; immunosuppressive function; mesenchymal stem cells; oncolytic virotherapy; oncolytic virus; tumor tropism.

Figure 1.

Different sources of MSCs in humans. MSCs, mesenchymal stem cells.

Figure 2.

MSC carriers enhance anti-tumor efficacy of oncolytic virotherapy. (1) MSCs loaded with OVs. (2) MSCs provide a replication locale for OVs to produce more virus particles. (3) Tumor tropisms and immunosuppressive MSC functions facilitate precise OV targeting to tumor lesions. OVs infect tumor cells and release ‘dangerous’ signals. (4) OVs alter MSC cytokine profiles. (5) Cytokines induce immune cell migration to the TME. (6) NK activation. (7) DCs activation. (8) Tumor antigen specific T cell activation. OVs, oncolytic virus; DC, dendritic cell; MSCs, mesenchymal stem cells; DAMPs, danger-associated molecular patterns; PAMPs, Pathogen-associated molecular patterns; TAAs, tumor-associated antigens; TANs, tumor-associated neoantigens; NK, natural killer; TAM, tumor-associated macrophage; TME, tumor microenvironment.