{"title":"Ex vivo T cell differentiation in adoptive immunotherapy manufacturing: Critical process parameters and analytical technologies","authors":"","doi":"10.1016/j.biotechadv.2024.108434","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>ex vivo</em> 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.</p></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":null,"pages":null},"PeriodicalIF":12.1000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0734975024001289/pdfft?md5=cbd00ab2ac6a45fc7da67c77ecea09de&pid=1-s2.0-S0734975024001289-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology advances","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0734975024001289","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
采用免疫疗法治疗癌症和其他疾病前景广阔。最近的证据表明,通过富集治疗产品中分化程度较低的 T 细胞亚群,可以提高这些细胞疗法的疗效,因此需要能够通过调节 T 细胞分化来富集这些亚群的先进制造技术。研究表明,改变某些关键的工艺控制参数,如细胞因子、代谢物、氨基酸和培养环境,可以有效地操纵体内外培养的 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,我们将研究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。我们还讨论了现有技术的局限性,并倡导业界进一步努力建立更严格的关键工艺参数(CPPs),开发更多针对 T 细胞分化的在线/在线 PATs。这些进步对于生产更有效的采纳性免疫疗法产品至关重要。
期刊介绍:
Biotechnology Advances is a comprehensive review journal that covers all aspects of the multidisciplinary field of biotechnology. The journal focuses on biotechnology principles and their applications in various industries, agriculture, medicine, environmental concerns, and regulatory issues. It publishes authoritative articles that highlight current developments and future trends in the field of biotechnology. The journal invites submissions of manuscripts that are relevant and appropriate. It targets a wide audience, including scientists, engineers, students, instructors, researchers, practitioners, managers, governments, and other stakeholders in the field. Additionally, special issues are published based on selected presentations from recent relevant conferences in collaboration with the organizations hosting those conferences.