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A Novel Embryonic Stem Cell‐based Vaccine for the Prevention of Lung Cancer

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 comprised of allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing immune‐stimulatory granulocyte macrophage‐colony stimulating factor (GM‐CSF) successfully blocks the outgrowth of an implantable lung cancer (Lewis lung carcinoma; LLC) and lung tumors caused by 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 produce GM‐CSF is needlessly complicated, and intact live ESCs carry the hazard of generating embryomas/teratomas. Here, we report the successful application of an alternative prophylactic vaccine comprised of exosomes/microvesicles derived from murine ESCs engineered to produce GM‐CSF. The prophylactic potential of the exosomes against implanted (subcutaneous inoculation of LLC) and metastatic (tail vein injection of LLC) lung cancer was tested by immunizing mice with exosomes derived from ESCs. Vaccination of mice with the exosomes bearing GM‐CSF significantly slowed or blocked the outgrowth of LLC while control exosomes lacking GM‐CSF were ineffective. Examination of tumor‐infiltrating immune cells showed robust tumor‐reactive immune responses in mice vaccinated with the exosomes bearing GM‐CSF, including an increase in cytotoxic T cells and a decrease in immunosuppressive T regulatory cells. Overall, vaccination of mice with ESCs‐exo bearing GM‐CSF is very effective in preventing both implantable and metastatic lung tumors with no detectable toxicity. Therefore, we conclude that a similar vaccine derived from GM‐CSF‐expressing human ESCs may be applicable to humans with increased risk of developing lung cancer.