Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Paris, France.
J Immunother. 2011 Jan;34(1):65-75. doi: 10.1097/CJI.0b013e3181fe535b.
Dendritic cell-derived exosomes (Dex) are nanovesicles bearing major histocompatibility complexes promoting T-cell-dependent antitumor effects in mice. Two phase I clinical trials aimed at vaccinating cancer patients with peptide-pulsed Dex have shown the feasibility and safety of inoculating clinical-grade Dex, but have failed to show their immunizing capacity. These low immunogenic capacities have led us to develop second-generation Dex with enhanced immunostimulatory properties. Here, we show that interferon-γ is a key cytokine conditioning the dendritic cell to induce the expression of CD40, CD80, CD86, and CD54 on Dex, endowing them with direct and potent peptide-dependent CD8(+) T-cell-triggering potential in vitro and in vivo. In this study, we describe the clinical grade process to manufacture large-scale interferon-γ-Dex vaccines and their quality control parameters currently used in a phase II trial.
树突状细胞衍生的外泌体（Dex）是一种带有主要组织相容性复合物的纳米囊泡，可促进小鼠的 T 细胞依赖性抗肿瘤作用。两项旨在用肽脉冲 Dex 接种癌症患者的 I 期临床试验已经证明了接种临床级 Dex 的可行性和安全性，但未能证明其免疫原性。这些低免疫原性使我们开发了具有增强免疫刺激特性的第二代 Dex。在这里，我们表明干扰素-γ是一种关键细胞因子，可以调节树突状细胞诱导 Dex 上 CD40、CD80、CD86 和 CD54 的表达，使它们具有直接和有效的肽依赖性 CD8(+)T 细胞触发潜力，无论是在体外还是体内。在这项研究中，我们描述了制造大规模干扰素-γ-Dex 疫苗的临床级工艺及其目前在 II 期试验中使用的质量控制参数。
