Somatically mutated tumor antigens in the quest for a more efficacious patient-oriented immunotherapy of cancer

Zlatko Trajanoski, Cristina Maccalli, Daniele Mennonna, Giulia Casorati, Giorgio Parmiani, Paolo Dellabona

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Although cancer immunotherapy shows efficacy with adoptive T cell therapy (ACT) and antibody- based immune checkpoint blockade, efficacious therapeutic vaccination of cancer patients with tumorassociated antigens (TAAs) remains largely unmet. Current cancer vaccines utilize nonmutated shared TAAs that may have suboptimal immunogenicity. Experimental evidence underscores the strong immunogenicity of unique TAAs derived from somatically mutated cancer proteins, whose massive characterization has been precluded until recently by technical limitations. The development of cost-effective, high-throughput DNA sequencing approaches makes now possible the rapid identification of all the somatic mutations contained in a cancer cell genome. This method, combined with robust bioinformatics platforms for T cell epitope prediction and established reverse immunology approaches, provides us with an integrated strategy to identify patientspecific unique TAAs in a relatively short time, compatible with their potential use in the clinic. Hence, it is now for the first time possible to quantitatively define the patient’s unique tumor antigenome and exploit it for vaccination, possibly in combination with ACT and/or immune checkpoint blockade to further increase immunotherapy efficacy.

Original languageEnglish
Pages (from-to)99-104
Number of pages6
JournalCancer Immunology, Immunotherapy
Volume64
Issue number1
DOIs
Publication statusPublished - 28 Aug 2015
Externally publishedYes

    Fingerprint

Keywords

  • Immunotherapy
  • NIBIT 2013
  • Oncogenomics
  • Somatic mutations
  • Tumor antigens
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this