Autologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer. T cell-based immunotherapy or sipuleucel-T therapy has yielded certain beneficial responses and a slight improvement on the overall survival of patients with metastatic castration-resistant prostate cancer (mCRPC) as shown in some clinical trials, suggesting that prostate cancer is immunoresponsive. In this study, we developed an adaptive cytokine-induced killer cell (CIK)-based immunotherapeutic application targeting the prostate cancer stem-like cells (PCSCs). In this therapeutic platform, dendritic cells (DC) were isolated from the peripheral blood mononuclear cells (PBMCs) and preloaded or sensitized with immunogenic peptides derived from two PCSC-associated cell membrane molecules, CD44 and EpCAM, followed by co-culture with the expanded peripheral blood lymphocyte (PBL)-derived CIK cells. The in vitro cytotoxic activity of DC-activated CIK cells against PCSCs was determined by CCK8 and TUNEL assays, and the in vivo anti-tumor effect of DC-activated CIK cells on prostate cancer xenograft tumors was evaluated in subcutaneous and orthotopic xenograft models. Our results showed that the peptide-sensitized DC-CIK cell preparation manifested significant in vitro cytotoxic activity against the PCSC-enriched prostatospheroids and also in vivo anti-tumor effect against prostate cancer xenografts derived from the PCSC-enriched prostatospheroids. Together, our established immunogenic peptide-sensitized DC-CIK-based cell preparation platform manifests its potential immunotherapeutic application in targeting the PCSCs and also prostate cancer.

中文翻译：

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通过基于免疫原性肽致敏的树突状细胞-细胞因子诱导的杀伤细胞的免疫治疗平台靶向前列腺癌干样细胞。

自体细胞免疫疗法或免疫增强疗法已证明对前列腺癌具有一些有希望的益处。如一些临床试验所示，基于T细胞的免疫疗法或sipuleucel-T疗法已产生某些有益的反应，并且对转移性去势抵抗性前列腺癌（mCRPC）患者的总体存活率略有改善，这表明前列腺癌具有免疫反应性。在这项研究中，我们开发了针对前列腺癌干样细胞（PCSCs）的基于适应性细胞因子诱导的杀伤细胞（CIK）的免疫治疗应用程序。在此治疗平台中，从外周血单核细胞（PBMC）中分离树突状细胞（DC），并预加载或敏化了衍生自两个PCSC相关细胞膜分子CD44和EpCAM的免疫原性肽，然后与扩增的外周血淋巴细胞（PBL）衍生的CIK细胞共培养。通过CCK8和TUNEL分析确定DC活化的CIK细胞对PCSC的体外细胞毒性活性，并在皮下和原位异种移植模型中评估DC活化的CIK细胞对前列腺癌异种移植肿瘤的体内抗肿瘤作用。我们的结果表明，肽敏化的DC-CIK细胞制剂对富含PCSC的前列腺球蛋白具有明显的体外细胞毒性活性，并且还对源自富含PCSC的前列腺球蛋白的前列腺癌异种移植物具有体内抗肿瘤作用。一起，我们建立的基于免疫原性肽的DC-CIK致敏的细胞制备平台展示了其在靶向PCSC和前列腺癌中的潜在免疫治疗应用。