INSERM, CHU Nantes, Nantes Université, Centre de Recherche en Transplantation et Immunologie UMR1064, ITUN, Nantes, France.
CHU Nantes, Unité de Therapie Cellulaire et Genique, Nantes, France.
Transplantation. 2021 Apr 1;105(4):832-841. doi: 10.1097/TP.0000000000003315.
Kidney transplantation is the therapeutic of choice for patients with kidney failure. While immunosuppressive drugs can control graft rejection, their use is associated with increased infections and cancer, and they do not effectively control chronic graft rejection. Cell therapy is an attractive strategy to minimize the use of pharmacological drugs.
We recently developed a protocol to generate human monocyte-derived autologous tolerogenic dendritic cells (ATDCs) from healthy volunteers. Herein, we transferred the ATDC manufacturing protocol to a Good Manufacturing Practice (GMP)-compliant facility. Furthermore, we compared the phenotype and in vitro functions of ATDCs generated from patients with end-stage renal disease to those generated from healthy volunteers.
We describe the critical steps for GMP-compliant production of ATDCs and define the quality criteria required to allow release of the cell products. Furthermore, we showed that ATDCs generated from healthy volunteers and patients with kidney failure display the same tolerogenic profile based on their phenotype, resistance to maturation, and ability to modulate T-cell responses.
Together, these results allowed us to define the production process and the quality criteria for the release of ATDCs before their administration in patients receiving a kidney transplant.
肾移植是肾衰竭患者的治疗选择。虽然免疫抑制药物可以控制移植物排斥反应，但它们的使用与感染和癌症风险增加有关，并且不能有效控制慢性移植物排斥反应。细胞疗法是一种减少药物使用的有吸引力的策略。
我们最近开发了一种从健康志愿者中生成人单核细胞来源的自体耐受性树突状细胞（ATDCs）的方案。在此，我们将 ATDC 制造方案转移到符合良好生产规范（GMP）的设施中。此外，我们比较了来自终末期肾病患者和健康志愿者的 ATDCs 的表型和体外功能。
我们描述了符合 GMP 的 ATDC 生产的关键步骤，并定义了允许放行细胞产品所需的质量标准。此外，我们表明，来自健康志愿者和肾衰竭患者的 ATDCs 在表型、对成熟的抗性和调节 T 细胞反应的能力方面表现出相同的耐受性特征。
这些结果使我们能够定义 ATDCs 的生产过程和放行质量标准，然后再将其施用于接受肾移植的患者。
