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

Luigi Aurisicchio, Erika Salvatori, Lucia Lione, Silvio Bandini, Matteo Pallocca, Roberta Maggio, Maurizio Fanciulli, Francesca De Nicola, Frauke Goeman, Gennaro Ciliberto, Antonella Conforti, Laura Luberto, Fabio Palombo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number78
JournalJournal of Experimental and Clinical Cancer Research
Volume38
Issue number1
DOIs
Publication statusPublished - Feb 14 2019

Keywords

  • Affinity
  • Cancer vaccine
  • Electroporation
  • Immunotherapy
  • Neoantigen
  • T cells
  • Vaccination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Aurisicchio, L., Salvatori, E., Lione, L., Bandini, S., Pallocca, M., Maggio, R., Fanciulli, M., De Nicola, F., Goeman, F., Ciliberto, G., Conforti, A., Luberto, L., & Palombo, F. (2019). Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth. Journal of Experimental and Clinical Cancer Research, 38(1), [78]. https://doi.org/10.1186/s13046-019-1084-4