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