Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy

• 作者: Zhi-di He Meng Zhang Yong-hui Wang Yang He Hai-rui Wang Bin-fan Chen Bin Tu Si-qi Zhu Yong-zhuo Huang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（9）
• 所属期刊栏目: Pharmaceutics
• 页码范围: 1516-1523
• 页数: 8页
• 语种: 英文

摘要

Immune checkpoint blockade therapy has become a first-line treatment in various cancers.But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy.How to increase their treatment efficacy is an urgent and clinically unmet need.It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity.Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor,compared with monotherapy.Here,we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1,and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1.P-Lipo increases intratumoral drug accumulation and promotes DC maturation,and thereby facilitates adaptive immune responses against tumor growth.The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ,and the reduced CD4+Foxp3+ regulatory T cells (Tregs).Collectively,the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.