A lung cancer vaccine based on exosomes of induced pluripotent stem cells

A lung cancer vaccine based on exosomes of induced pluripotent stem cells ABSTRACT 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, probably due to their focus on inducing immune responses against individual lung tumor-associated antigens. If a lung cancer vaccine targets multiple antigens present only in lung tumors, but not in normal adult tissues, 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 that are absent 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. Exploiting the antigenic similarity between tumor cells and iPSCs, we propose to thoroughly investigate efficacy of a 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+ T cell-dependent immune responses and eradicating lung TICs. In this grant, we will investigate this hypothesis in two clinically relevant, immunocompetent murine lung tumor models. Two specific aims are proposed: 1) Investigate the translational potential of iPSC-exo vaccination against lung cancer; 2) Elucidate the mechanism by which iPSC-exo vaccination prevents lung cancer. We believe that the success of proposed experiments will lead to clinical trials of a similar vaccine against human pulmonary malignancy.