A new immune-nanoplatform for promoting adaptive antitumor immune response

被引:27
作者
Merino, Maria [1 ,4 ]
Contreras, Ana [1 ,4 ]
Casares, Noelia [2 ,4 ]
Troconiz, Inaki F. [1 ,4 ]
ten Hagen, Timo L. M. [3 ]
Berraondo, Pedro [2 ,4 ]
Zalba, Sara [1 ,4 ]
Garrido, Maria J. [1 ,4 ]
机构
[1] Univ Navarra, Sch Pharm, Dept Pharm & Pharmaceut Technol, Pamplona, Spain
[2] CIMA, Program Immunol & Immunotherapy, Pamplona, Spain
[3] Erasmus MC, Lab Expt Oncol, Rotterdam, Netherlands
[4] Navarra Inst Hlth Res IdisNA, Navarra, Spain
关键词
Liposome; Immunoliposome; PD-L1; PEG; Coupling method; Immunotherapy; LIPOSOMAL DOXORUBICIN; SIGNALING PATHWAYS; IMMUNOLIPOSOMES; CANCER; PD-L1; IMMUNOTHERAPY; EXPRESSION; CHALLENGES; MOLECULES; ANTI-PD-1;
D O I
10.1016/j.nano.2018.12.016
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Immunoliposomes (ILs), obtained with monoclonal antibodies (mAbs) decorating the liposome surface, are used for cancer treatment. These mAbs provide the recognition of molecules upregulated in cancer cells, like Programmed Death-Ligand 1 (PD-L1), an immune-checkpoint involved in tumor resistance, forming a complex that blocks this molecule and thereby, induces antitumor immune response. This mechanism introduces a new concept for ILs. ILs coupled to anti-PD-L1 or its Fab' fragment have been developed and in vitro/in vivo characterized. Factors such as coupling methods, PEG density and ligand size were optimized. In vitro data showed that Fab'-ILs displayed the highest PD-L1 cell interaction, correlating with a higher in vivo tumor accumulation and an increase of effector cytotoxic CD8(+) T cells, providing tumor shrinkage and total regression in 20% of mice. Therefore, a novel immune-nanoplatform able to modulate the immune system has been developed, allowing the encapsulation of several agents for combinatorial therapies. (C) 2019 Elsevier Inc. All rights reserved.
引用
收藏
页码:13 / 25
页数:13
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