|
KMID : 0923620210210060044
|
|
Immune Network
2021 Volume.21 No. 6 p.44 ~ p.44
|
|
|
Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes
|
|
Kim Sang-Hyun
Park Ha-Eun
Jeong Seong-Un
Moon Jun-Hyeok
Lee Young-Ran
Lee Young-Ran
Kim Jeong-Ki
Kong Hyun-Seok
Park Chan-Su
Lee Chong-Kil
|
|
|
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-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). 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-2Kb 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.
|
|
|
KEYWORD
|
|
|
Polymeric nanoparticle, Tumor peptide, Peptide-MHC-I complex, Tumor vaccine, Cytotoxic T lymphocyte, Anti-tumor activity
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|
|