Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth

J Exp Clin Cancer Res. 2019 Feb 14;38(1):78. doi: 10.1186/s13046-019-1084-4.


Background: Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine.

Methods: In an effort to develop potent and efficacious neoantigen-based vaccines, we have developed different neoantigen minigene (NAM) vaccine vectors to determine the rules for a successful neoantigen cancer vaccine (NCV) delivered by plasmid DNA and electroporation. Immune responses were analyzed at the level of single neoantigen by flow cytometry and correlated with tumor growth. Adoptive T cell transfer, from HLA-2.1.1 mice, was used to demonstrate the efficacy of the NCV pipeline against human-derived tumors.

Results: In agreement with previous bodies of evidence, immunogenicity was driven by predicted affinity. A strong poly-functional and poly-specific immune response was observed with high affinity neoantigens. However, only a high poly-specific vaccine vector was able to completely protect mice from subsequent tumor challenge. More importantly, this pipeline - from the selection of neoantigens to vaccine design - applied to a new model of patient derived tumor xenograft resulted in therapeutic treatment.

Conclusions: These results suggest a feasible strategy for a neoantigen cancer vaccine that is simple and applicable for clinical developments.

Keywords: Affinity; Cancer vaccine; Electroporation; Immunotherapy; Neoantigen; T cells; Vaccination.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology*
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precision Medicine / methods*
  • Xenograft Model Antitumor Assays


  • Antigens, Neoplasm
  • Cancer Vaccines