Adoptive immunotherapy shows great promise as a treatment for cancer and other diseases. Recent evidence suggests that the therapeutic efficacy of these cell-based therapies can be enhanced by the enrichment of less-differentiated T cell subpopulations in the therapeutic product, giving rise to a need for advanced manufacturing technologies capable of enriching these subpopulations through regulation of T cell differentiation. Studies have shown that modifying certain critical process control parameters, such as cytokines, metabolites, amino acids, and culture environment, can effectively manipulate T cell differentiation in ex vivo cultures. Advanced process analytical technologies (PATs) are crucial for monitoring these parameters and the assessment of T cell differentiation during culture. In this review, we examine such critical process parameters and PATs, with an emphasis on their impact on enriching less-differentiated T cell population. We also discuss the limitations of current technologies and advocate for further efforts from the community to establish more stringent critical process parameters (CPPs) and develop more at-line/online PATs that are specific to T cell differentiation. These advancements will be essential to enable the manufacturing of more efficacious adoptive immunotherapy products.

中文翻译：

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过继免疫疗法生产中的离体 T 细胞分化：关键工艺参数和分析技术


过继免疫疗法作为癌症和其他疾病的治疗方法显示出巨大的前景。最近的证据表明，这些基于细胞的疗法的治疗效果可以通过在治疗产品中富集低分化的 T 细胞亚群来增强，从而需要能够通过调节 T 细胞分化来富集这些亚群的先进制造技术。研究表明，修改某些关键过程控制参数，如细胞因子、代谢物、氨基酸和培养环境，可以有效控制离体培养中的 T 细胞分化。先进的过程分析技术 （PAT） 对于监测这些参数和评估培养过程中的 T 细胞分化至关重要。在这篇综述中，我们研究了这些关键过程参数和 PAT，重点是它们对富集低分化 T 细胞群的影响。我们还讨论了当前技术的局限性，并倡导社区进一步努力建立更严格的关键工艺参数 （CPP） 并开发更多特定于 T 细胞分化的在线/在线 PAT。这些进步对于生产更有效的过继免疫治疗产品至关重要。