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, Ha-Eun Park, Seong-Un Jeong, Jun-Hyeok Moon, Young-Ran Lee, Jeong-Ki Kim, Hyunseok Kong, Chan-Su Park, and Chong-Kil Lee. 2021. “Induction of Peptide-Specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes.” Immune Network 21 (6). https://doi.org/10.4110/in.2021.21.e44.
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.
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