We hypothesize that human embryonic stem cells represent a potentially scalable source of human dendritic cells that could be used to treat a wide array of diseases including HIV/AIDS and cancer. In fact dendritic cell based therapies have shown some promise in early trials, but they are largely limited by the numbers of cells available for treatment protocols. We propose here to develop a potentially unlimited source of human dendritic cells from human embryonic stem cells. More importantly, we propose to modify these cells to express a novel cell surface molecule that can be used for targeted delivery of specific proteins. Ultimately we envision using these cells to direct primary immune responses. The studies described in this SEED proposal are directed towards HIV specific immune responses, but would be widely applicable to other pathogen-based diseases, as well to tumor associated antigens.
Dendritic cell immunization, dendritic cell-based gene therapies and immunotherapies are being explored as treatments for a number of diverse human diseases, particularly in settings that are refractory to conventional therapies. Unfortunately, these protocols are directly limited by the ability to generate sufficient quantities of dendritic cells ex vivo. Human embryonic stem cells represent a potentially scalable source of dendritic cells that could be used in these settings. For instance, they could be used for the prevention and treatment of pathogen based diseases such as HIV/AIDS, Hepatitis C and Influenza. In addition, development of a source of self renewing dendritic cells could dramatically advance patient specific protocols for the treatment of cancer. Taken together these diseases and their treatments impact Californians personally and economically. The development of improved treatment and prevention modalities by harnessing the potential of human embryonic stem cells would represent a major benefit to the lives of all Californians.