Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy

Biomaterials. 2018 Aug:174:54-66. doi: 10.1016/j.biomaterials.2018.05.015. Epub 2018 May 10.

Abstract

Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and CpG onto LDH nanoparticles. Using melanoma as the model cancer and Tyrosinase-related protein 2 (Trp2) peptide as the model antigen, we demonstrated that dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth in comparison with aggregated LDH-based vaccine. We further constructed multi-target dispersion-stable LDH-based vaccine by co-loading Trp2, two mutated epitopes (M27 and M30) and CpG, which showed remarkable inhibition of melanoma growth. These results suggest that dispersion-stable LDH nanoparticles are an ideal platform to load multi-antigens and immune stimulants as effective personalized therapeutic cancer vaccines.

Keywords: Colloidal stability; Layered double hydroxides; Melanoma; Personalized immunotherapy; Therapeutic cancer vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigens, Neoplasm / drug effects
  • Biological Transport
  • Cancer Vaccines / genetics
  • Cancer Vaccines / pharmacology
  • Cell Line, Tumor
  • Epitopes / genetics
  • Epitopes / pharmacology*
  • Female
  • Humans
  • Hydroxides / chemistry*
  • Immunotherapy / methods
  • Intramolecular Oxidoreductases / pharmacology
  • Melanoma / drug therapy*
  • Mice, Inbred C57BL
  • Mutation / drug effects
  • Nanoparticles / chemistry*
  • Particle Size
  • Signal Transduction
  • Surface Properties
  • T-Lymphocytes, Cytotoxic / immunology
  • Tissue Distribution

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Hydroxides
  • Intramolecular Oxidoreductases
  • dopachrome isomerase