Recombinant programmed cell death protein 1 functions as an immune check point blockade and enhances anti-cancer immunity
Recombinant programmed cell death protein 1 functions as an immune check point blockade and enhances anti-cancer immunity
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重组程序性细胞死亡蛋白1发挥免疫检查点阻断作用并增强抗癌免疫力
DOI：
10.1016/j.biomaterials.2022.121550
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发表时间：
2022-05-06
期刊：
影响因子：
14
通讯作者：
Jin, Jun-O
中科院分区：
文献类型：
--
作者：
Hwang, Juyoung;An, Eun-Koung;Jin, Jun-O
有效的癌症治疗不仅要治疗原发肿瘤，还要治疗转移性和复发性肿瘤。免疫检查点阻断介导的免疫治疗显示出良好的肿瘤治疗效果；然而，它对转移性或复发性癌症的作用仍然有限。在这里，我们提取了重组小鼠程序性死亡-1 （rmPD-1）蛋白。提取的rmPD-1有效结合到表达PD-L1和PDL2的CT-26和4T1细胞上。rmPD-1不改变树突状细胞（dc）的活化；然而，rmPD-1促进了T细胞介导的针对CT-26肿瘤的抗癌免疫。此外，rmPD-1修饰的热响应杂交纳米颗粒（piHNPs）在808 nm激光照射下促进了CT-26细胞的凋亡和坏死细胞死亡，从而增强了对小鼠CT-26第一次攻击肿瘤的抗肿瘤作用。此外，pihnp介导的第一次攻击CT-26的治愈小鼠也可以阻止第二次攻击的肺转移瘤的生长，这依赖于癌症抗原特异性记忆T细胞免疫。研究还证实，piHNP还能阻止第2次4T1攻击乳腺癌在第1次4T1攻击治愈小鼠中的肺转移生长。因此，这些数据表明，rmPD-1作为一种免疫检查点阻断剂可用于肿瘤的治疗，piHNPs可能是一种预防癌症转移和复发的新型治疗剂。
Effective cancer therapy aims to treat not only primary tumors but also metastatic and recurrent cancer. Immune check point blockade-mediated immunotherapy showed promising effect against tumors; however, it still has a limited effect in metastatic or recurrent cancer. Here, we extracted recombinant murine programmed death-1 (rmPD-1) proteins. The extracted rmPD-1 effectively bound to CT-26 and 4T1 cells expressing PD-L1 and PDL2. The rmPD-1 did not alter the activation of dendritic cells (DCs); however, rmPD-1 promoted T cellmediated anti-cancer immunity against CT-26 tumors in mice. Moreover, rmPD-1 decorated thermal responsive hybrid nanoparticles (piHNPs) promoted apoptotic and necrotic cell death of CT-26 cells in response to laser irradiation at 808 nm consequently, it promoted anti-tumor effects against the 1st challenged CT-26 tumors in mice. In addition, piHNP-mediated cured mice from 1st challenged CT-26 was also prevented the 2nd challenged lung metastatic tumor growth, which was dependent of cancer antigen-specific memory T cell immunity. It was also confirmed that the lung metastatic growth of 2nd challenged 4T1 breast cancer was also prevented in cured mice from 1st challenged 4T1 by piHNP. Thus, these data demonstrate that rmPD-1 functions as an immune checkpoint blockade for the treatment of tumors, and piHNPs could be a novel therapeutic agent for preventing cancer metastasis and recurrence.