期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 36, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202104068
关键词
adoptive cell transfer; cancer immunotherapy; dendritic cells; nanovaccines; neoantigens
类别
资金
- National Natural Science Foundation of China [81903548, 81690265, 81803444, 81521005, 32070927]
- Youth Innovation Promotion Association of CAS [2019283]
- Shandong Provincial Natural Science Foundation [ZR2019ZD25]
- International Partnership Program of CAS [153631KYSB20190013]
- Shanghai Sailing Program [19YF1457300]
The combination of neoantigen-loaded nanovaccines and adoptive dendritic cell transfer enhances personalized immunity by facilitating immune cell access to lymph nodes and inhibiting tumor growth.
Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens' access to resident DCs and DCs' access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.
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