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Research Article

Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer

Tianyuan Xue1,§, Zhirang Zhang1,§, Tianliang Fang1,§, Baoqi Li1, Yuan Li1, Liyan Li1, Yanghua Jiang3, Fangfang Duan1, Fanqiang Meng1(), Xin Liang2(), Xudong Zhang1()
Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Stem Cell and Regenerative Tissue Engineering, School of Basic Medical Sciences, Guangdong Medical University, Dongguan 523808, China
The First People’s Hospital of Chenzhou, Chenzhou 423000, China

§ Tianyuan Xue, Zhirang Zhang, and Tianliang Fang contributed equally to this work.

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In this work, we genetically engineered cell membrane vesicles expressing anti-programmed celldeath-1 (aPD-1) single-chain variable fragment antibody (aPD-1-scFv) and loading CPI-444to reinvigorate exhausted T cells for cancer immunotherapy.

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.

Keywords

drug deliveryA2a receptor PD-1 receptorcancer immunotherapy

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5295-5304
DOI: 10.1007/s12274-022-4182-0
Cite this article:
Xue T, Zhang Z, Fang T, et al. Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer. Nano Research, 2022, 15(6): 5295-5304. https://doi.org/10.1007/s12274-022-4182-0
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