B-106 Development of anti-tumor cytotoxic lymphocytes using engineered human primary blood dendritic cells

Abstract

Dendritic cell (DC)-based immunotherapy has achieved modest clinical benefits, however, several technical hurdles in DC preparation, activation and cancer-associated antigen (TAA) delivery limit its broad applications in cancer therapy. We have developed immortalized and activated human primary blood dendritic cell (DC) lines, ihv-DCs. Human primary blood dendritic cells can be immortalized from several cc of peripheral blood and can be expanded at large quantity at normal cell culture condition. The ihv-DCs are a subset of CD11c+/CD205+ DCs that persistently display co-stimulatory molecules and produce interferon gamma. These DCs are engineered to constitutively express a TAA such as hTERT, which prime donor-derived T cells to generate antigen-specific CTLs that induce cytolysis of hTERT-expressing target cells in an HLA-A2-restricted manner. In addition, the engineered DCs are able to induce simultaneous production of both anti-cancer CTLs and NK cells from naive PBMCs. In NSG mouse model, infusion of the activated CTLs and NK cells that are generated from naive PBMCs using the engineered DCs suppress lung metastasis of human lung cancer cells. Both CTLs and NK cells are found to infiltrate lung as well as lymphoid tissues, mimicking the in vivo trafficking patterns of cytotoxic lymphocytes. This new approach should facilitate the development of cell-based immunotherapy for human lung cancer.