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

Autor: Kavitha Yaddanapudi, Shuhan Meng, Aaron G. Whitt, Numan Al Rayyan, Jamaal Richie, Allison Tu, John W. Eaton, Chi Li
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: OncoImmunology, Vol 8, Iss 3 (2019)
Druh dokumentu: article
ISSN: 2162-402X
2162402X
DOI: 10.1080/2162402X.2018.1561119
Popis: 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.
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