Center for Public Health Research, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
Y-Clone Medical Science Co. Ltd., Suzhou, China.
Acta Biomater. 2020 Jun;109:21-36. doi: 10.1016/j.actbio.2020.04.015. Epub 2020 Apr 13.
Chimeric antigen receptor (CAR) therapy has achieved remarkable clinical efficacy against hematological cancers and has been approved by FDA for treatment of B-cell tumors. However, the complex manufacturing process and limited success in solid tumors hamper its widespread applications, thus prompting the development of new strategies for overcoming the abovementioned hurdles. In the last decade, nanotechnology has provided sustainable strategies for improving cancer immunotherapy through vaccine development and delivery of immunomodulatory drugs. Nanotechnology can boost CAR-T therapy and may overcome the existing challenges by emerging as a carrier for CAR-T therapy or in combination with CAR-T, it may inhibit solid tumors more effectively than conventional approaches. The revealing of cellular mechanisms, barriers and potential strategies that could be used to manipulate and/or modify cells would enable unprecedented advances in nanotechnology for biologics delivery. This review outlines the journey and barriers of nanoparticles (NPs) across the cell. Subsequently, the approaches to tackle the barriers and strategies to modulate NPs as a carrier for CAR-T therapy are discussed. Finally, the role of NPs in CAR-T therapy and the potential challenges are summarized. This review aims to provide the readers with a detailed overview of NP-based CAR-T therapy research and distil this information into an accessible form conducive to design desired CAR-T therapy using NP approach. STATEMENT OF SIGNIFICANCE: Chimeric antigen receptor (CAR) T-cell therapy is the most vibrant field in immuno-oncology today, with enormous benefits to patients with B-cell malignancies. However, a rapid and straightforward procedure for CAR-T generation is an exigent need to broaden its therapeutic avenue. Nanotechnology has emerged as a novel alternative approach for CAR-T generation. To the best of our knowledge, this is the first in-depth review that briefly highlights the various aspects of nanotechnology in CAR-T therapy, including the strategies to brand NPs as an effective carrier for CAR cargo, its potential advantages, challenges, and future roadmap. It provides readers with a detailed overview of NP-based CAR-T therapy research, and researchers would be able to distill this information into an accessible form conducive to design the desired CAR therapy using the nanotechnology approach.
嵌合抗原受体 (CAR) 疗法在治疗血液系统恶性肿瘤方面取得了显著的临床疗效，并已获得 FDA 批准用于治疗 B 细胞肿瘤。然而，其复杂的制造工艺和在实体瘤中疗效有限限制了其广泛应用，因此需要开发新的策略来克服上述障碍。在过去的十年中，纳米技术通过疫苗开发和免疫调节药物的递送来为改善癌症免疫疗法提供了持续的策略。纳米技术可以增强 CAR-T 疗法的疗效，并可能通过作为 CAR-T 疗法的载体或与 CAR-T 联合使用来克服现有挑战，从而比传统方法更有效地抑制实体瘤。揭示细胞机制、障碍和潜在策略，这些策略可用于操纵和/或修饰细胞，将使生物技术传递的纳米技术取得前所未有的进展。本综述概述了纳米颗粒 (NP) 穿越细胞的历程和障碍。随后，讨论了克服障碍的方法和将 NP 作为 CAR-T 疗法载体进行修饰的策略。最后，总结了 NP 在 CAR-T 疗法中的作用和潜在挑战。本综述旨在为读者提供基于 NP 的 CAR-T 疗法研究的详细概述，并将这些信息提炼成易于理解的形式，有利于使用 NP 方法设计理想的 CAR-T 疗法。
嵌合抗原受体 (CAR) T 细胞疗法是当今免疫肿瘤学最具活力的领域，为 B 细胞恶性肿瘤患者带来了巨大的益处。然而，快速而直接的 CAR-T 生成程序是扩大其治疗途径的迫切需要。纳米技术已成为 CAR-T 生成的一种新的替代方法。据我们所知，这是第一篇深入综述，简要强调了纳米技术在 CAR-T 疗法中的各个方面，包括将 NPs 标记为 CAR 有效载体的策略、其潜在优势、挑战和未来路线图。它为读者提供了基于 NP 的 CAR-T 疗法研究的详细概述，研究人员将能够将这些信息提炼成易于理解的形式，有利于使用纳米技术方法设计理想的 CAR 疗法。
