Kim, Gi Beom Sung, Hyo-Dong Nam, Gi-Hoon Kim, Wonjun Kim, Seohyun Kang, Dayeon Lee, Eun Jung Kim, In-San 2024-01-19T14:33:48Z 2024-01-19T14:33:48Z 2022-01-10 2021-05-10 0168-3659 https://pubs.kist.re.kr/handle/201004/116998 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. English ELSEVIER H-FERRITIN EXPRESSION NIVOLUMAB PD-L1 Design of PD-1-decorated nanocages targeting tumor-draining lymph node for promoting T cell activation Article 10.1016/j.jconrel.2021.03.038 1 JOURNAL OF CONTROLLED RELEASE, v.333, pp.328 - 338 JOURNAL OF CONTROLLED RELEASE 333 328 338 scie scopus 000651627800001 2-s2.0-85103563350 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article H-FERRITIN EXPRESSION NIVOLUMAB PD-L1 Nanocage Surface engineering PD-1 PD-L blockade Tumor-draining lymph node Drug delivery