Dendritic cell-directed vaccination with a lentivector encoding PSCA for prostate cancer in mice.
Dendritic cell-directed vaccination with a lentivector encoding PSCA for prostate cancer in mice.
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DOI：
10.1371/journal.pone.0048866
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Xiao L;Joo KI;Lim M;Wang P
前列腺干细胞抗原（PSCA）在前列腺肿瘤组织中的高表达，特别是在某些转移性组织中的高表达，使其成为一个有吸引力的免疫治疗靶点。在这项研究中，我们评估了树突状细胞（DC）导向的慢病毒载体（DCLV）编码鼠PSCA（DCLV-PSCA）作为一种新的肿瘤疫苗在小鼠模型中的前列腺癌。我们发现DCLV-PSCA可以优先将PSCA抗原基因递送到表达DC-SIGN的293 T细胞和骨髓来源的DC（BMDC）。在雄性C57 BL/6小鼠中用DCLV-PSCA直接免疫在体内引发了稳健的PSCA应答性CD 8+和CD 4 + T细胞。在转基因腺癌小鼠前列腺细胞系（TRAMP-C1）协同肿瘤模型中，我们进一步证明了DCLV-PSCA疫苗接种的小鼠在预防性模型中可免受致死性肿瘤攻击，而在治疗性模型中观察到肿瘤生长较慢。该DCLV-PSCA疫苗还显示出使用表达PSCA的B16-F10模型抑制肿瘤转移的功效。总之，这些数据表明，DCLV是PSCA在提供抗前列腺癌免疫方面的有效疫苗载体。
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.
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