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Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells

Embryonic stem cells (ESCs) are pluripotent stem cells capable of self-renewal and differentiation into all types of embryonic cells. Like many other cell ...

University of Louisville

The antigenic similarity between embryos and tumors has raised the idea of using embryonic material as a preventative vaccine against neoplastic disease. Indeed, we have previously reported that a vaccine comprises allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing GM-CSF (to amplify immune responses) successfully blocks the outgrowth of an implantable cancer (Lewis lung carcinoma; LLC) and lung tumors generated in mice using a combination of a mutagen followed by chronic pulmonary inflammation. However, such a vaccine is obviously impractical for application to humans. The use of fibroblasts to generate GM-CSF is needlessly complicated, and intact whole ESCs carry the hazard of generating embryomas/teratomas. Here, we report the successful application of an alternative prophylactic vaccine comprises exosomes derived from murine ESCs engineered to produce GM-CSF. Vaccination of mice with these exosomes significantly slowed or blocked the outgrowth of implanted LLC while control exosomes lacking GM-CSF were ineffective. Examination of tumor-infiltrating immune cells from mice vaccinated with the GM-CSF-expressing exosomes showed robust tumor-reactive CD8 T effector responses, Th1 cytokine responses, and higher CD8 T effector/CD4CD25Foxp3 T regulatory cell ratio in the tumors. We conclude that a similar vaccine derived from GM-CSF- expressing human ESCs can be employed as a preventative vaccine for humans with an increased risk of developing cancer.

Allison Tu

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