Induction of antitumor cytotoxic lymphocytes using engineered human primary blood dendritic cells

Significance The dendritic cell (DC) is the master regulator of host immunity. The results of our study bring significant technical improvements in DC methodology. First, a method was developed to expand primary blood DCs at unlimited amounts. Second, the established DCs are constitutively activated and readily available to prime naïve T cells. Third, the DCs can be genetically modified to deliver given tumor antigens in high efficiency and to express activating molecules in driving simultaneous production of antigen-specific T cells and natural killer (NK) cells. Fourth, introducing two allogeneic DRB1 molecules into the DCs improves generation of tumor antigen-specific T cells. Further, the DC-activated cytotoxic T lymphocytes and NK cells potently suppress tumor growth and metastasis in human lung cancer mouse models.