Journal
NANO LETTERS
Volume 21, Issue 22, Pages 9410-9418Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c02582
Keywords
cell membrane vesicles; cancer vaccine; cancer immunotherapy; aptamer targeting; immune checkpoint blockade
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Funding
- National Basic Research Programs of China (973 Program) [2016YFA0201200]
- National Natural Science Foundation of China [51525203, 51761145041]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 program from the Ministry of Education of China
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Researchers have designed a targeted nanovaccine that can induce DC maturation and trigger strong antitumor immune responses through assembly of functional DNA. Combining CMV-based nanovaccines with immune checkpoint blockade can improve therapeutic responses and generate long-term immune memory.
By inducing tumor-specific immune responses, tumor vaccines have recently aroused great research interest. Herein, we design a targeted nanovaccine by equipping cell membrane vesicles (CMVs) harvested from tumor cells with functional DNA including CpG oligonucleotide, an agonist for toll-like receptor 9, as well as an aptamer targeting the dendritic cell (DC)specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) receptor overexpressed on DCs. Such DNA-modified CMVs could target DCs and further stimulate their maturation. Notably, our nanovaccines could trigger robust antitumor immune responses to effective delay the tumor growth. Moreover, the combination of CMV-based nanovaccines with an immune checkpoint blockade could result in improved therapeutic responses by eliminating the majority of the tumors as well as long-term immune memory to prevent tumor recurrence. Therefore, by simply assembling functional DNA on CMVs harvested from tumor cells, we propose a general platform of DC-targeted personalized cancer vaccines for effective and specific cancer immunotherapy.
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