dendritic cell-directed vaccination with a lentivector encoding psca for prostate cancer in mice树突cell-directed接种lentivector编码psca在小鼠前列腺癌.pdfVIP

Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice 1 1 1 1,2,3 Liang Xiao , Kye-Il Joo , Matthew Lim , Pin Wang * 1 Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America, 2 Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States of America, 3 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States of America Abstract Many studies have demonstrated that prostate stem cell antigen (PSCA) is an attractive target for immunotherapy based on its overexpression in prostate tumor tissue, especially in some metastatic tissues. In this study, we evaluated dendritic cell (DC)-directed lentiviral vector (DCLV) encoding murine PSCA (DCLV-PSCA) as a novel tumor vaccine for prostate cancer in mouse models. We showed that DCLV-PSCA could preferentially deliver the PSCA antigen gene to DC-SIGN-expressing 293T cells and bone marrow-derived DCs (BMDCs). Direct immunization with the DCLV-PSCA in male C57BL/6 mice elicited robust PSCA-responsive CD8+ and CD4+ T cells in vivo. In a transgenic adenocarcinoma mouse prostate cell line (TRAMP-C1) synergetic tumor model, we further demonstrated that DCLV-PSCA-vaccinated mice could be protected from lethal tumor challenge in a prophylactic model, whereas slower tumor growth was observed in a therapeutic model. This DCLV-PSCA vaccine also showed efficacy in inhibiting tumor metastases using a PSCA-expressing B16-F10 model. Taken together, these data suggest that DCLV is a potent vaccine carrier for PSCA in delivering anti-prostate cancer imm