Human Embryonic Stem Cell Derivatives as Cancer Therapeutics

Abstract

Dendritic cells (DCs) play a central role as bridges between innate and adaptive immunity and are the most potent antigen presenting cells essential for initiating adaptive immune responses. Autologous DC-based therapy is being established as a novel modality for cancer treatment. To move from expensive individualized vaccines to more generally applicable cancer vaccine formulations, we have derived DCs from human embryonic stem cells (hESCs). We then investigated expression of transgene in our DCs using baculoviral vectors. After successful gene transfer for enforced up-regulation of CD1d, we demonstrated that administration of these genetically modified DCs could significantly improve the function of DCs in survival of animals in a mouse breast cancer model. This result indicates that baculoviral engineering hESC of derivatives can possibly be used as scalable and broadly applicable cancer therapeutics. In view of the significance of DCs in antitumor immunity and emerging applications of stem cells as cancer-targeting vectors to treat tumors, we studied in the second part of the project whether mesenchymal stem cells (MSCs) and neural stem cells (NSCs), including MSCs and NSCs derived from hESCs, affect the activity of DCs. After comparing inhibitory effects of human MSCs and NSCs on generation, differentiation and functions of human DCs, we observed that NSCs displayed less immunosuppressive activity than MSCs. Therefore, a balanced consideration between tumor targeting properties and immune-regulatory functions should be given when hESC derivatives are used for cancer therapy.