Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1
10.16438/j.0513-4870.2021-0967
- VernacularTitle:肿瘤微环境响应脂质体阻断CXCL12/CXCR4通路协同增加抗PD-L1的免疫疗效
- Author:
Ru-dong WANG
1
,
2
;
Yi-wei PENG
1
,
2
;
Zhen-zhen YANG
1
,
2
;
Yi-tian DU
1
,
2
;
Meng LIN
1
,
2
;
Qi SUN
1
,
2
;
Xian-rong QI
1
,
2
Author Information
1. School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Beijing 100191, China
- Publication Type:Research Article
- Keywords:
liposome;
small interfering ribonucleic acid;
C-X-C chemokine ligand 12 / C-X-C chemokine receptor type 4;
programmed cell death protein 1 / programmed death receptor-ligand 1;
matrix metalloproteinase-2
- From:
Acta Pharmaceutica Sinica
2022;57(1):178-187
- CountryChina
- Language:Chinese
-
Abstract:
Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.
