免疫疗法
癌症免疫疗法
癌症研究
自愈水凝胶
材料科学
癌症
纳米技术
医学
内科学
高分子化学
作者
Di Zhang,Qian Li,Xiangwu Chen,Xinxin Nie,Fumin Xue,Wei Xu,Yuxia Luan
出处
期刊:Small
[Wiley]
日期:2022-07-17
卷期号:18 (32)
被引量:13
标识
DOI:10.1002/smll.202202663
摘要
T cell exhaustion caused by mitochondrial dysfunction is the major obstacle of T cells-based cancer immunotherapy. Besides exhausted T cells, the insufficient major histocompatibility complex class I (MHC I) on tumor cells leads to inefficient T cell recognition of tumor cells, compromising therapeutic efficacy. Therapeutic platform to regulate T cell exhaustion and MHC I expression for boosting T cells-based cancer immunotherapy has not been realized up to date. Herein, an injectable hydrogel is designed to simultaneously tune T cell exhaustion and MHC I expression for amplified cancer immunotherapy. The hydrogel is in situ constructed in tumor site by utilizing oxidized sodium alginate-modified tumor cell membrane vesicle (O-TMV) as a gelator, where axitinib is encapsulated in the lipid bilayer of O-TMV while 4-1BB antibody and proprotein convertase subtilisin/kexin type 9 inhibitor PF-06446846 nanoparticles are present in the cavities of hydrogel. After immune response trigged by O-TMV antigen, the 4-1BB antibody-promoted T cell mitochondrial biogenesis and the axitinib-lowered hypoxia synergistically reverse T cell exhaustion while the PF-06446846-amplified MHC I expression facilitates T cell recognition of tumor cells, demonstrating a powerful immunotherapeutic efficacy. This strategy on reprograming T cell exhaustion and improving T cell potency offers new concept for T cells-based cancer immunotherapy.
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