Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal.
Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal.
复制标题
DOI：
10.1186/s12951-021-00975-5
复制
发表时间：
2021-08-12
影响因子：
10.2
通讯作者：
Dong J
中科院分区：
文献类型：
--
作者：
Wang Z;Chen L;Ma Y;Li X;Hu A;Wang H;Wang W;Li X;Tian B;Dong J
由于现有治疗方法的局限性，脊柱转移瘤的临床治疗仍然是一个巨大的挑战。程序性细胞死亡蛋白1（PD 1）/程序性细胞死亡配体1（PD-L1）通路阻断已被探索为一种有前途的免疫策略;然而，它们的抑制具有低应答率，导致最小的细胞毒性T细胞浸润。为了改善难治性肿瘤的免疫抑制微环境，进一步提高免疫治疗的疗效，我们报道了一种由上转换纳米颗粒核和大孔介孔二氧化硅壳（UCMS）组成的全方位介孔纳米载体，其同时负载光敏剂分子、IDO衍生肽疫苗AL-9和PD-L1抑制剂。IDO衍生肽可被树突状细胞识别并呈递给CD 8+细胞毒性T细胞，从而增强免疫应答并促进IDO表达的肿瘤细胞的杀伤。同时，近红外（NIR）激活的光动力疗法（PDT）可诱导免疫原性细胞死亡（ICD），从而促进效应T细胞的浸润。通过结合PDT引发的ICD、肽疫苗和免疫检查点阻断，设计的UCMS@ Pep-aPDL 1成功增强了局部和全身的抗肿瘤免疫力，并减少了转移灶的进展，证明了癌症免疫治疗的协同策略。 在线版本包含补充材料，可通过10.1186/s12951-021-00975-5获得。
The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy. The online version contains supplementary material available at 10.1186/s12951-021-00975-5.
登录
查看更多内容
影响因子：
8.4
作者：
Chen L;Zhao T;Zhao M;Wang W;Sun C;Liu L;Li Q;Zhang F;Zhao D;Li X
通讯作者：
Li X
影响因子：
16.8
作者：
Munn DH;Mellor AL
通讯作者：
Mellor AL
DOI：
10.1038/s41577-019-0269-6
发表时间：
2020-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Irvine DJ;Dane EL
通讯作者：
Dane EL
影响因子：
2.3
作者：
Conlon, Kevin C.;Miljkovic, Milos D.;Waldmann, Thomas A.
通讯作者：
Waldmann, Thomas A.
影响因子：
2.8
作者：
Adogwa, Owoicho;Rubio, Daniel R.;Jennings, Jack W.
通讯作者：
Jennings, Jack W.