医学
奥沙利铂
免疫疗法
结直肠癌
免疫系统
癌症
抗体
免疫原性细胞死亡
癌症免疫疗法
癌症研究
不利影响
免疫检查点
抗原
药理学
内科学
免疫学
作者
Linfu Chen,Lin Zhang,Rui Zhao,Jingjing Shen,Yingyao Wang,Jiafei Zhu,Huapan Fang,Nanhui Liu,Cheng Wang,Ting Wei,Yu Shuang Chai,Maoyi Li,Chenghao Wu,Qian Chen,Zhuang Liu
出处
期刊:Nano Today
[Elsevier]
日期:2023-06-01
卷期号:50: 101834-101834
被引量:8
标识
DOI:10.1016/j.nantod.2023.101834
摘要
Despite the approval of immune checkpoint blockade (ICB) for colorectal cancer treatment, its objective response rate remains to be improved, especially for non-immunogenic tumors. Moreover, systemically administrated ICB antibodies is usually associated with immune-related adverse effects (irAEs). Herein, we report novel oral administration of anti-programmed cell death protein L1 (anti-PD-L1) complexes for immunotherapy against colorectal tumors. Antibodies could form nanocomplexes with fluorocarbon modified chitosan (FCS) to acquire greatly improved transmucosal penetration ability, owing to the ability of FCS to reduce mucus binding and temporary open tight junctions between epithelial cells. As evidenced in orthotopic colorectal tumors on mice, orally administrated FCS/anti-PD-L1 nanocomplexes exhibited greatly improved intestinal permeability and significant intertumoral penetration, and if combined with oxaliplatin (OXA) chemotherapy to induce an immunogenic tumor phenotype, could finally inhibit the growth of tumors and prolong the animal survival. Notably, compared to systematic injection of anti-PD-L1, oral administration of FCS/anti-PD-L1 achieved comparable therapeutic efficacy with five-fold dosage, and exhibited reduced tendency of systemic irAEs as exhibited by the decreased percentage of Th17 cells in lymph nodes. Our work here provides a simple but effective strategy for immunotherapy by oral administration of ICB antibodies, achieving strong antitumor immune responses without the concern of systemic irAEs.
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