Lentiviral-siRNA blockade of immunosuppressive genes increases DC vaccine efficacy.

Abstract Dendritic cells (DCs) play an essential role in the activation of T cells. Because of their potent activation capabilities, DCs have been used to stimulate anti-tumor responses via vaccines. While these vaccines have elicited immune responses, they have not been curative. In a tumor environment, suppressive factors can downregulate their ability to generate effective responses through modifying gene expression in DCs. We have been identifying such genes and proposed that blocking them in DCs would enhance their efficacy. To test our hypothesis, we silenced one immunosuppressive gene using a lenti viral vector siRNA construct. Our results demonstrate that blocking gene expression enhances activation and anti-tumor responses, leading to prolonged survival of tumor bearing mice. This approach may serve as a novel means to increase the efficacy of ex vivo developed DC vaccines.