Necroptotic cancer cells-mimicry nanovaccine boosts anti-tumor immunity with tailored immune-stimulatory modality

被引：86

作者：

Kang, Ting ^{[1
]}

Huang, Yukun ^{[1
]}

Zhu, Qianqian ^{[1
]}

Cheng, Hao ^{[3
]}

Pei, Yuanyuan ^{[1
]}

Feng, Jingxian ^{[1
]}

Xu, Minjun ^{[1
]}

Jiang, Gan ^{[2
]}

Song, Qingxiang ^{[2
]}

Jiang, Tianze ^{[1
]}

Chen, Hongzhuan ^{[2
]}

Gao, Xiaoling ^{[2
]}

Chen, Jun ^{[1
]}

机构：

[1] Fudan Univ, Sch Pharm, Minist Educ, Key Lab Smart Drug Delivery, Lane 826,Zhangheng Rd, Shanghai 201203, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Dept Pharmacol & Chem Biol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China

[3] Shanghai Jiao Tong Univ, Bio X Inst, Shanghai 200240, Peoples R China

来源：

BIOMATERIALS | 2018年 / 164卷

基金：

中国国家自然科学基金;

关键词：

Biomimetic nanotechnology; Anticancer vaccines; HSP70 functional peptide; Anti-PD-1; therapy; NK cells; TUMOR MICROENVIRONMENT; NK CELLS; CHECKPOINT BLOCKADE; ADVANCED MELANOMA; DENDRITIC CELLS; LUNG-CANCER; IMMUNOTHERAPY; NANOPARTICLES; THERAPY; DELIVERY;

D O I：

10.1016/j.biomaterials.2018.02.033

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC). Necroptotic tumor cells can release danger associated molecule patterns (DAMPs) like heat shock proteins, being more immunogenic than naive tumor cells. Here, nano-size "artificial necroptotic cancer cell" (alpha HSP70p-CM-CaP) composing of phospholipid bilayer and a phosphate calcium core was designed as a flexible vaccine platform for co-delivering cancer membrane proteins (CM), DAMPs signal augmenting element alpha-helix HSP70 functional peptide (alpha HSP70p) and CpG to both natural killer (NK) cells and APC. Mechanically, immunogenic B16OVA tumor cells membrane-associated antigens and alpha HSP70p were reconstituted in artificial outer phospholipid bilayer membrane via one-step hydration and CpG encapsulated in the phosphate calcium core. The resulted alpha HSP70p-CM-CaP exhibited 30 nm in diameter with the immunogenic membrane proteins reserved in the particles to produce synergistic effect on bone marrow derived dendritic cells maturation and antigen-presentation. Following alpha HSP70p-CM-CaP vaccination, efficient lymph node trafficking and multi-epitope-T cells response was observed in mice. Vitally, alpha HSP70p-CM-CaP was also able to induce expansion of IFN-gamma-expressing CD8(+) T cells and NKG2D(+) NK cells subsets. Most promisingly, alpha HSP70p-CM-CaP vaccination led to the killing of target cells and tumor regression in vivo when combined with anti-PD-1 antibody treatment on mice B16OVA melanoma models. Altogether, we demonstrated proof-of-concept evidence for the feasibility, capability and safety of a nanovaccine platform towards efficient personalized anticancer application. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：80 / 97

页数：18

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