Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice

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 immunity.

Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances hepatitis B virus-specific immune responses <italic>in vivo</italic>

“…It has been found that f.p. (footpad area) injections of LVs induced much higher responses than the intramuscular area injection, subcutaneous area injection, and intraperitoneal injection [49]. It is speculated that administering by the f.p.…”

“…It is speculated that administering by the f.p. route provides LVs a better chance to encounter DCs [49]. Direct administration of lentiviral vectors encoding TAA gene induced more potent TAA-specific immune responses when compared with the DCs that were transduced with lentiviral vectors ex vivo [50].…”

Targeted nonviral gene therapy in prostate cancer

“…[90][91][92] Many studies have used genes encoding specific prostate antigens to induce an immunoresponse directed against prostate cancer cells only. Xiao et al 94 used lentivirus to deliver PSCA to prostate cancer. They reported a significant increase in CD8 + and CD4 + T cells after injecting the drug into mice.…”

Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

“…By pseudotyping a LV with this mutated Sindbis virus derived envelope glycoprotein, targeted infection of murine DCs after direct subcutaneous administration was achieved. Moreover, this elicited strong and therapeutic antigen specific immune responses [5,[103][104][105]. Besides genetic alterations, the viral surface can also be chemically engineered to alter the binding specificity.…”