PD-L1 siRNA-hyaluronic acid conjugate for dual-targeted cancer immunotherapy
- Authors
- Kim, Suyeon; Heo, Roun; Song, Seok Ho; Song, Kwon-Ho; Shin, Jung Min; Oh, Se Jin; Lee, Hyo-Jung; Chung, Jo Eun; Park, Jae Hyung; Kim, Tae Woo
- Issue Date
- 6월-2022
- Publisher
- ELSEVIER
- Keywords
- Tumor foreignization; Immune evasion; Tumor microenvironment; PD-L1; CD44
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.346, pp.226 - 239
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 346
- Start Page
- 226
- End Page
- 239
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/143024
- DOI
- 10.1016/j.jconrel.2022.04.023
- ISSN
- 0168-3659
- Abstract
- Foreignization " of tumor cells via delivery of a non-self foreign antigen (Ag) into tumors is an appealing strategy to initiate anti-tumor immunity that can facilitate tumor rejection by pre-existing foreign-Ag-reactive T cells. However, the immune-suppressive factors in the tumor microenvironment (TME) limit the durable and potent immune response of these cells against tumor antigens, stressing the need for improved tumor-foreignization strategies. Here, we demonstrate that blockade of programmed cell death ligand 1 (PD-L1) on both tumor cells and dendritic cells (DCs) can markedly potentiate the induction of tumor-reactive T cells, thereby strengthening the anti-tumor immunity ignited by tumor-foreignization. Specifically, we developed a polymeric nanoconjugate (PEG-HA-OVA/PPLs), consisting of siPD-L1-based polyplexes, PEGylated hyaluronic acid as the CD44-targeting moiety, and ovalbumin (OVA) as a model foreign antigen. Notably, PEG-HA-OVA/PPLs were simultaneously delivered into CD44high tumor cells and CD44high DCs, leading to efficient cross-presentation of OVA and downregulation of PD-L1 in both cell types. Importantly, the nanoconjugate not only allowed OVA specific T cells to vigorously reject the foreignized tumor cells but also reprogrammed the TME to elicit robust T-cell responses specific to the endogenous tumor Ags, eventually generating long-lasting protective immunity. Thus, our combination strategy represents an innovative approach for the induction of potent tumor immunity via a two-step consecutive immune boost against exogenous and endogenous tumor Ags.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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