A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8+ T-cell-mediated anti-tumor immunity

J Control Release. 2014 Jan 10:173:158-65. doi: 10.1016/j.jconrel.2013.10.027. Epub 2013 Oct 29.

Abstract

PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-ε-caprolactone) (PEG-b-PLACL), Span®85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b)-restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-γ-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy.

Keywords: Adjuvant; Cervical cancer; CpG oligodeoxynucleotide; Human papillomavirus (HPV); Immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Emulsions / chemistry
  • Emulsions / therapeutic use
  • Female
  • Hexoses / chemistry
  • Hexoses / immunology
  • Hexoses / therapeutic use
  • Human papillomavirus 16 / immunology*
  • Immunotherapy
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / therapeutic use*
  • Papillomavirus E7 Proteins / chemistry
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus E7 Proteins / therapeutic use*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology
  • Polyesters / chemistry
  • Polyesters / therapeutic use
  • Squalene / chemistry
  • Squalene / immunology
  • Squalene / therapeutic use
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / therapy*
  • Uterine Cervical Neoplasms / virology

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cancer Vaccines
  • Emulsions
  • Hexoses
  • Oligodeoxyribonucleotides
  • Papillomavirus E7 Proteins
  • Polyesters
  • oncogene protein E7, Human papillomavirus type 16
  • lactide-caprolactone copolymer
  • Squalene
  • sorbitan trioleate