Targeted gene delivery systems for T-cell engineering.

IF 4.9 2区 医学 Q2 CELL BIOLOGY
Cellular Oncology Pub Date : 2024-10-01 Epub Date: 2024-05-16 DOI:10.1007/s13402-024-00954-6
Fengling Wang, Yong Huang, JiaQian Li, Weilin Zhou, Wei Wang
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Abstract

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

Abstract Image

用于 T 细胞工程的靶向基因传递系统。
T 淋巴细胞是宿主系统抵御病原体、肿瘤和环境威胁不可或缺的细胞。利用 T 淋巴细胞的细胞毒性特性消灭抗原特异性细胞的治疗潜力既明显又有效。基因工程 T 细胞,如 CAR-T 和 TCR-T 细胞疗法中使用的 T 细胞,已在治疗癌症和自身免疫性疾病方面取得了显著的临床疗效。然而,目前 T 细胞基因工程的主要策略是必须进行体外 T 细胞分离和修饰,这就增加了复杂性并延长了基于 T 细胞的免疫疗法的开发时间。本综述探讨了为 T 细胞设计的基因递送系统的复杂性,包括病毒载体和非病毒载体。病毒载体以转导效率高而著称,但也面临着很大的局限性,如潜在的免疫原性和大规模生产的复杂性。相反,非病毒载体具有更安全的特性和可规模化生产的潜力,但其转导效率往往较低。基因递送系统无需分离就能实现对 T 细胞的定向基因转移,是该领域的一大进步。这篇综述评估了这类系统的设计原理和目前的研究进展,强调了体内基因修饰疗法的潜力,这种疗法可能会彻底改变基于 T 细胞的治疗方法。通过对这些系统进行全面分析,我们希望为 T 细胞免疫疗法的未来发展提供有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cellular Oncology
Cellular Oncology ONCOLOGY-CELL BIOLOGY
CiteScore
10.30
自引率
1.50%
发文量
86
审稿时长
12 months
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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