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T 细胞模拟纳米颗粒用于癌症免疫治疗。

T-Cell-Mimicking Nanoparticles for Cancer Immunotherapy.

机构信息

Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

出版信息

Adv Mater. 2020 Oct;32(39):e2003368. doi: 10.1002/adma.202003368. Epub 2020 Aug 18.

Abstract

Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70-80% of patients. To address some of the challenges faced by the current cancer treatments, here T-cell-membrane-coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T-cell-membrane-originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas-ligand-mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor-β1 (TGF-β1)) and programmed death-ligand 1 (PD-L1) of cancer cells by scavenging TGF-β1 and PD-L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti-tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen-nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.

摘要

癌症免疫疗法,包括过继性 T 细胞转移和免疫检查点阻断,最近在癌症治疗中显示出了相当大的成功。然而,由于免疫抑制性肿瘤微环境,转移的 T 细胞常常变得衰竭。相比之下,免疫检查点阻断可以使衰竭的 T 细胞重新焕发活力;然而,在 70-80%的患者中,其治疗效果并不显著。为了解决当前癌症治疗所面临的一些挑战,这里开发了 T 细胞膜包覆的纳米颗粒(TCMNPs)用于癌症免疫治疗。类似于细胞毒性 T 细胞,TCMNPs 可以通过 T 细胞膜起源的蛋白靶向肿瘤,并通过释放抗癌分子和诱导 Fas 配体介导的细胞凋亡来杀死癌细胞。与细胞毒性 T 细胞不同,TCMNPs 通过清除 TGF-β1 和 PD-L1 来抵抗癌细胞的免疫抑制分子(例如转化生长因子-β1(TGF-β1))和程序性死亡配体 1(PD-L1)。事实上,TCMNPs 在黑色素瘤治疗中的疗效高于免疫检查点阻断。此外,TCMNPs 在以抗原非特异性方式治疗肺癌中的抗肿瘤作用也得到了证实。总之,TCMNPs 有可能改善当前的癌症免疫疗法。

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