@article{Xue2022, 
author = {Tianyuan Xue and Zhirang Zhang and Tianliang Fang and Baoqi Li and Yuan Li and Liyan Li and Yanghua Jiang and Fangfang Duan and Fanqiang Meng and Xin Liang and Xudong Zhang},
title = {Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer},
year = {2022},
journal = {Nano Research},
volume = {15},
number = {6},
pages = {5295-5304},
keywords = {drug delivery, A2a receptor, PD-1 receptor, cancer immunotherapy},
url = {https://www.sciopen.com/article/10.1007/s12274-022-4182-0},
doi = {10.1007/s12274-022-4182-0},
abstract = {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 A2a adenosine 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.}
}