A Lung Cancer Vaccine Using Exosomes for Induced Pluripotent Stem Cells. – PI: Chi Li

A critical challenge in lung cancer research is to develop innovative vaccines to protect against pulmonary malignancy. Recent efforts to develop lung cancer vaccines have largely failed, probablydue to their focus on inducing immune responses against individual lung cancer-associated antigens.If a lung cancer vaccine targets multiple antigens present only in lung tumors, but not in normal adulttissues, the chance of success will be greatly improved. Induced pluripotent stem cells (iPSCs) are reprogrammed from somatic cells and have the capacity of self-renewing and developing into all cell types of the adult body. It is known that iPSCs and tumor cells share carcinoembryonic antigens which could be classified as neoantigens due to their absence in normal adult tissues. Lung tumors also contain a subpopulation of tumor-initiating cells (TICs) with high tumorigenicity and self-renewal capability that contribute to the resistance to conventional therapies. To exploit the antigenic similarity between tumor cells and iPSCs, we propose to thoroughly investigate efficacy of an anti-lung cancer vaccine composed of exosomes from murine iPSCs expressing granulocyte-macrophage colony stimulating factor (GM-CSF) as an immunostimulatory adjuvant (iPSC-exo). We hypothesize that iPSC-exo vaccination prevents lung tumorigenesis by triggering CD8-dependent immune responses and eradicating lung TICs. In this grant, we will investigate this hypothesis in a clinically relevant primary lung adenocarcinoma model of immunocompetent mice. Two specific aims are envisioned: 1) Investigate the translational potential of iPSC-exo vaccination against primary lung adenocarcinoma in mice; 2) Elucidate the mechanism by which iPSC-exo vaccine prevents lung adenocarcinoma. We believe that the success of proposed experiments will lead to clinical trials of a similar vaccine against human pulmonary malignancy.