Immune Netw.  2021 Dec;21(6):e44. 10.4110/in.2021.21.e44.

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

• Kim SH
• Park HE
• Jeong SU
• Moon JH
• Lee YR
• Kim JK
• Kong H
• Park CS
• Lee CK

• KMID: 2523805
• DOI: http://doi.org/10.4110/in.2021.21.e44

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 halflife 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 SIINFEKLspecific 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