Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer
Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer
复制标题
DOI：
10.1007/s12274-022-4182-0
复制
发表时间：
2022-03
期刊：
影响因子：
9.9
通讯作者：
Tianyuan Xue;Zhirang Zhang;Tian-Liang Fang;Baoqi Li;Yuan Li;Liyan Li;Yanghua Jiang;Fangfang Duan;Fanqiang Meng;Xin Liang;Xudong Zhang
中科院分区：
文献类型：
--
作者：
Tianyuan Xue;Zhirang Zhang;Tian-Liang Fang;Baoqi Li;Yuan Li;Liyan Li;Yanghua Jiang;Fangfang Duan;Fanqiang Meng;Xin Liang;Xudong Zhang
癌细胞异常表达免疫抑制性检查点配体并产生导致T细胞耗竭的某些代谢物。免疫检查点阻断（ICB）疗法可以重振疲惫的T细胞，在临床癌症治疗中取得了令人印象深刻的反应。然而，有限的临床反应率和肿瘤外毒性限制了ICB治疗。本文中，制备展示抗程序性细胞死亡-1（PD-1）单链可变片段抗体（aPD-1-scFv）的细胞囊泡以重振T细胞免疫力以对抗癌症。展示aPD-1-scFv的纳米囊泡（aPD-1-scFv NV）可以通过PD-1阻断增强T细胞的抗肿瘤活化。此外，负载A2 a腺苷受体（A2 aR）拮抗剂CPI-444的NV辅助T细胞拮抗腺苷，腺苷是由癌细胞产生的免疫抑制代谢物。因此，CPI-444负载的aPD-1-scFv NV可以强烈增加肿瘤浸润T细胞的密度和活性，直接抑制肿瘤的进展和转移。
Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion. Immune checkpoint blockade (ICB) therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment. However, the limited clinical response rate and off-tumor toxicities restrict ICB therapy. Herein, cellular vesicles displaying anti-programmed cell death-1 (PD-1) single-chain variable fragment antibody (aPD-1-scFv) were prepared to reinvigorate T cell immunity to counteract cancer. The nanovesicles displaying aPD-1-scFv (aPD-1-scFv NVs) could enhance the anti-tumor activation of T cells through PD-1 blockade. Furthermore, NVs loading the A2aadenosine receptor (A2aR) antagonist CPI-444 assisted T cells to antagonize adenosine, an immunosuppressive metabolite produced by cancer cells. Hence, CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells, directly restraining tumor progress and metastasis.