Induction of antitumor immunity by vaccination of dendritic cells transfected with MUC1 RNA

Dendritic cells (DC) are potent APCs, In this study, murine bone marrow-der ived DC were transfected with RNA encoding the MUC1 Ag that is aberrantly o verexpressed in human breast and other carcinomas. The MUC1 RNA-transfected DC exhibited cell surface expression of MUC1 and costimulatory molecules, After injection at the base of the tail, the transfected DC were detectable in inguinal lymph nodes by dual immunochemical staining. Vaccination of wi ld-type mice with MUC1 RNA-transfected DC induced anti-MUC1 immune response s against MUC1-positive MC38/MUC1, but not MUC1-negative, tumor cells. Mice immunized with the transfected DC were protected against challenge with MC 38/MUC1 tumor cells, Furthermore, mice with established MC38/MUC1 tumors we re eliminated after receiving the vaccination. CTLs isolated from mice immu nized with the transfected DC exhibited specific cytolytic activity against MC38/MUC1 tumor cells. In contrast to these findings, there was little if any anti-MUC1 immunity induced with the transfected DC in MUC1 transgenic ( MUC1.Tg) mice. However, coadministration of the transfected DC and IL-12 re versed the unresponsiveness to MUC1 Ag in MUC1.Tg mice and induced MUC1-spe cific immune responses, These findings demonstrate that vaccination of DC t ransfected with MUC1 RNA and IL-12 reverses tolerance to MUC1 and induces i mmunity against MUC1-positive tumors.