Design of PD-1-decorated nanocages targeting tumor-draining lymph node for promoting T cell activation
- Authors
- Kim, Gi Beom; Sung, Hyo-Dong; Nam, Gi-Hoon; Kim, Wonjun; Kim, Seohyun; Kang, Dayeon; Lee, Eun Jung; Kim, In-San
- Issue Date
- 10-5월-2021
- Publisher
- ELSEVIER
- Keywords
- Drug delivery; Nanocage; PD-1; PD-L blockade; Surface engineering; Tumor-draining lymph node
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.333, pp.328 - 338
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 333
- Start Page
- 328
- End Page
- 338
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/137381
- DOI
- 10.1016/j.jconrel.2021.03.038
- ISSN
- 0168-3659
- Abstract
- Targeted delivery of immunomodulatory molecules to the lymph nodes is an attractive means of improving the efficacy of anti-cancer immunotherapy. In this study, to improve the efficacy of PD-1 blockade-based therapy, nanocages were designed by surface engineering to decorate a programmed cell death protein 1 (PD-1) that is capable of binding against programmed death-ligand 1 (PD-L1) and -ligand 2 (PD-L2). This nanocage-mediated multivalent interaction remarkably increases the binding affinity and improves the antagonistic activity compared to free soluble PD-1. In addition, with the desirable nanocage size for optimal tumor-draining lymph node (TDLN) targeting (approximately 20 nm), rapid draining and increased accumulation into the TDLNs were observed. Moreover, the interference of the PD-1/PD-L axis with ultra-high affinity in the tumor microenvironment (effector phase) and the TDLNs (cognitive phase) significantly enhances the dendritic cell-mediated tumor-specific T cell activation. This characteristic successfully inhibited tumor growth and induced complete tumor eradication in some mice. Thus, the delivery of immunomodulatory molecules with nanocages can be a highly efficient strategy to achieve stronger anti-tumor immunity.
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