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Nanotechnology-Based CAR-T Strategies for Improving Efficacy and Safety of Tumor Immunotherapy

机译：基于纳米技术的CAR-T策略，提高肿瘤免疫疗法的疗效和安全性

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摘要

Therapeutic responses to chimeric antigen receptor (CAR) T cell therapy in patients with limited treatment options have been appealing in several clinical trials. However, the efficacy of CAR-T therapy has been challenged by several obstacles when treating patients with solid tumors, such as severe toxicities, restricted access to tumor sites, suboptimal therapeutic persistence, and manufacturing issues. Nanotechnology has the advantages of protecting CAR-T cells from being suppressed by tumor microenvironment (TME) and favorably adapting immune-modulating drugs' pharmacokinetics by modifying their spatiotemporal release profiles. Loaded with nanoparticles and packed onto CAR-T cells, immune-modulating drugs can be delivered to the tumor site and lymph node more efficiently, stimulating the expansion and activity of CAR-T cells. To protect normal tissues from the nonspecific toxicity of the activated CAR-T cells, formulations are optimized toward tumor targeting delivery of nanotechnology. This review summarizes the nanotechnology strategies to improve the safety and efficacy of CAR-T therapy. In addition, the unsolved problems existing in the clinical application of CAR-T therapy are focused on, where study and exploration by the way of nanotechnology is needed.
机译：治疗抗原受体（CAR）T细胞疗法在有限的治疗方案患者中对患者进行了治疗反应，在几种临床试验中一直吸引。然而，当治疗固体肿瘤的患者，如严重毒性，限制肿瘤部位，次优治疗持久性和制造问题时，Car-T治疗的疗效受到几种障碍的挑战。纳米技术具有保护Car-T细胞免受肿瘤微环境（TME）抑制的优点，并通过改变它们的时空释放型材来利益地适应免疫调节药物药代动力学。装载纳米颗粒并填充到Car-T细胞上，免疫调节药物可以更有效地递送至肿瘤部位和淋巴结，刺激Car-T细胞的膨胀和活性。为了保护来自活化的Car-T细胞的非特异性毒性的正常组织，配方朝向靶向纳米技术递送的肿瘤进行了优化。本综述总结了纳米技术策略，以提高汽车-T治疗的安全性和功效。此外，需要在临床应用中存在的未解决的问题，主要是纳米技术的研究和勘探。

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