Multi-antigen DNA vaccine delivered by polyethylenimine and Salmonella enterica in neuroblastoma mouse model

Cancer Immunol Immunother. 2020 Dec;69(12):2613-2622. doi: 10.1007/s00262-020-02652-2. Epub 2020 Jun 27.

Abstract

Neuroblastoma is an example of a difficult-to-treat tumor with high incidence of relapse. DNA vaccination could be applied as a relapse prophylactic option for patients with high-risk neuroblastoma. Its efficacy depends directly on a target antigen of choice and a delivery method. Three neuroblastoma-associated antigens (tyrosine hydroxylase, Survivin, PHOX2B) and two delivery methods were investigated. Our data suggest that antigen PHOX2B is a more immunogenic target that induces cellular immune response and tumor regression more effectively than tyrosine hydroxylase and Survivin. Immunogenicity testing revealed that the delivery of DNA vaccine by Salmonella enterica was accompanied by a stronger immune response (cytotoxicity and IFNγ production) than that by DNA-polyethylenimine conjugate. Nevertheless, intramuscular immunization with PEI led to higher decrease of tumor volume compared to that after oral gavage with Salmonella vaccine.

Keywords: DNA vaccine; Neuroblastoma; PHOX2B; Polyethylenimine; Salmonella enterica.

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor / transplantation
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Injections, Subcutaneous
  • Mice
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neuroblastoma / immunology
  • Neuroblastoma / pathology
  • Neuroblastoma / therapy*
  • Polyethyleneimine / chemistry
  • Salmonella Vaccines / administration & dosage
  • Salmonella Vaccines / immunology*
  • Salmonella typhimurium / immunology
  • Survivin / genetics
  • Survivin / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / immunology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology

Substances

  • Antigens, Neoplasm
  • Birc5 protein, mouse
  • Cancer Vaccines
  • Drug Carriers
  • Homeodomain Proteins
  • Phox2b protein, mouse
  • Salmonella Vaccines
  • Survivin
  • Transcription Factors
  • Vaccines, Attenuated
  • Vaccines, DNA
  • Polyethyleneimine
  • Tyrosine 3-Monooxygenase