Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen

doi:10.1038/s41551-020-00624-6

	Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen
	Xie, Xiaoling 2,3; Hu, Yuxing 2; Ye, Tong 3,4; Chen, Yiran 2; Zhou, Lijuan 2; Li, Feng 3,4; Xi, Xiaobo 3,4; Wang, Shuang 3; He, Yanjie 2; Gao, Xiaoyong 3
刊名	NATURE BIOMEDICAL ENGINEERING
	2020-10-12
页码	19
ISSN号	2157-846X
DOI	10.1038/s41551-020-00624-6
英文摘要	The sustained release of a leukaemia-associated epitope peptide and of anti-PD-1 antibody co-encapsulated in degradable microcapsules results in superior therapeutic outcomes in mouse models of leukaemia. Therapeutic leukaemia vaccines have shown modest potency. Here, we show that the co-encapsulation of a leukaemia-associated epitope peptide highly expressed in leukaemia patients and of the immune checkpoint inhibitor anti-programmed-cell-death-protein-1 (anti-PD-1) in degradable poly(lactic acid) microcapsules resulted in the sustained release of the peptide and of the antibody, which led to the recruitment of activated antigen-presenting cells to the injection site, their uptake of the peptide and the transportation of the anti-PD-1 antibody to lymph nodes, enhancing the expansion of epitope-specific T cells and the activation of cytotoxic T cells. After single subcutaneous injections of vaccine formulations with different epitope peptides, mice bearing leukaemia xenografts derived from humanized cell lines or from primary cells from patients showed better therapeutic outcomes than mice receiving repeated injections of free antigen, antibody and a commercial adjuvant. The sustained release of a tumour-associated peptide and of anti-PD-1 may represent a generalizable strategy for boosting antitumour immune responses to leukaemia.
资助项目	National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[21622608] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29040303] ; National Key R&D Program of China[2017YFA0207900] ; Science and Technology Program of Guangzhou, China[201704020216] ; Natural Science Foundation of Guangdong Province, China[2018B030311042] ; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China[2018GZR110105014]
WOS关键词	ACUTE MYELOID-LEUKEMIA ; PEPTIDE VACCINE ; WT1 EXPRESSION ; RESPONSES ; LYMPHOCYTES ; GENERATION ; TRANSPLANTATION ; IMMUNOTHERAPY ; INHIBITION ; BLOCKADE
WOS研究方向	Engineering
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000577092600001
资助机构	National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; Science and Technology Program of Guangzhou, China ; Natural Science Foundation of Guangdong Province, China ; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/42316]
专题	中国科学院过程工程研究所
通讯作者	Wei, Wei; Ma, Guanghui; Li, Yuhua
作者单位	1.Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou, Peoples R China 2.Southern Med Univ, Zhujiang Hosp, Dept Hematol, Guangzhou, Peoples R China 3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Xie, Xiaoling,Hu, Yuxing,Ye, Tong,et al. Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen[J]. NATURE BIOMEDICAL ENGINEERING,2020:19.
APA	Xie, Xiaoling.,Hu, Yuxing.,Ye, Tong.,Chen, Yiran.,Zhou, Lijuan.,...&Li, Yuhua.(2020).Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen.NATURE BIOMEDICAL ENGINEERING,19.
MLA	Xie, Xiaoling,et al."Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen".NATURE BIOMEDICAL ENGINEERING (2020):19.