摘要
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 A_(2a)adenosine receptor(A_(2a)R)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.
基金
supported by grants from the National Natural Science Foundation of China(No.31971268)
the Natural Science Foundation of Guangdong Province(No.2020A1515010802)
Guangdong Basic and Applied Basic Research Foundation(No.2020A1515110166)
Shenzhen Excellent Science and Technology Innovation Talent Training Project(Excellent Youth Project,No.RCYX20200714114643121)
Science,Technology&Innovation Commission of Shenzhen Municipality(No.JCYJ20200109142610136)
Basic Research Program of Shenzhen(No.JCYJ20180507181654186)
Health System Scientific Research Project of Shenzhen Guangming District Science and Innovation Bureau(Nos.2020R01073,and 2020R01061)
Special Fund for Economic Development of Guangming District,Shenzhen(No.2021R01128)
University of Chinese Academy of Sciences-Shenzhen Hospital Research Funding(No.HRF2020004)
the Fundamental Research Funds for the Central Universities(No.19lgzd45)
Disciplinary Construction of Posts of Zhujiang Scholars(No.4SG21005G)
Discipline Construction Project of Guangdong Medical University(No.4SG21008G).
