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Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I ComplexesInduction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

Other Titles
Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes
Authors
Kim, Sang-HyunPark, Ha-EunJeong, Seong-UnMoon, Jun-HyeokLee, Young-RanKim, Jeong-KiKong, HyunseokPark, Chan-SuLee, Chong-Kil
Issue Date
12월-2021
Publisher
KOREA ASSOC IMMUNOLOGISTS
Keywords
Polymeric nanoparticle; Tumor peptide; Peptide-MHC-I complex; Tumor vaccine; Cytotoxic T lymphocyte; Anti-tumor activity
Citation
IMMUNE NETWORK, v.21, no.6, pp.1 - 15
Indexed
SCIE
SCOPUS
KCI
Journal Title
IMMUNE NETWORK
Volume
21
Number
6
Start Page
1
End Page
15
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/136666
DOI
10.4110/in.2021.21.e44
ISSN
1598-2629
Abstract
Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2K(b) molecules, and then the natural peptide epitopes associated with the H-2K(b) molecules were exchanged with a model tumor peptide, SIINFEKL (OVA(257-268)). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H-2K(b) complex-specific CD8(+) T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8(+) T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.
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