Exosomes from GM-CSF expressing embryonic stem cells are an effective prophylactic vaccine for cancer prevention

• Published in: Oncoimmunology Vol. 8; no. 3; p. 1561119
• Main Authors: Yaddanapudi, Kavitha, Meng, Shuhan, Whitt, Aaron G., Al Rayyan, Numan, Richie, Jamaal, Tu, Allison, Eaton, John W., Li, Chi
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 04-03-2019; Taylor & Francis Group
• Subjects: Cancer; embryonic stem cells; exosomes; Original Research; prophylactic vaccine; prophylactic vaccine; embryonic stem cells; exosomes; Cancer
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2018.1561119

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
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T effector/CD4
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CD25
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Foxp3
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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.