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

• Main Authors: Kavitha Yaddanapudi, Shuhan Meng, Aaron G. Whitt, Numan Al Rayyan, Jamaal Richie, Allison Tu, John W. Eaton, Chi Li
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-03-01
• Series: OncoImmunology
• Subjects: cancer; embryonic stem cells; exosomes; prophylactic vaccine
• Online Access: http://dx.doi.org/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+ T effector/CD4+CD25+Foxp3+ 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.