Tumor immunotherapy

Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors

Ornella Franzese, Francesco Torino, Maria Pia Fuggetta, Angelo Aquino, Mario Roselli, Enzo Bonmassar, Anna Giuliani, Stefania D'Atri

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

More than 40 years ago, we discovered that novel transplantation antigens can be induced in vivo or in vitro by treating murine leukemia with dacarbazine. Years later, this phenomenon that we called "Chemical Xenogenization" (CX) and more recently, "Drug-Induced Xenogenization" (DIX), was reproduced by Thierry Boon with a mutagenic/carcinogenic compound (i.e. N-methyl-N'-nitro-N-nitrosoguanidine). In both cases, the molecular bases of DIX rely on mutagenesis induced by methyl adducts to oxygen-6 of DNA guanine. In the present review we illustrate the main DIX-related immune-pharmacodynamic properties of triazene compounds of clinical use (i.e. dacarbazine and temozolomide). In recent years, tumor immunotherapy has come back to the stage with the discovery of immune checkpoint inhibitors (ICpI) that show an extraordinary immune-enhancing activity. Here we illustrate the salient biochemical features of some of the most interesting ICpI and the up-to-day status of their clinical use. Moreover, we illustrate the literature showing the direct relationship between somatic mutation burden and susceptibility of cancer cells to host's immune responses. When DIX was discovered, we were not able to satisfactorily exploit the possible presence of triazene-induced neoantigens in malignant cells since no device was available to adequately enhance host's immune responses in clinical settings. Today, ICpI show unprecedented efficacy in terms of survival times, especially when elevated mutation load is associated with cancer cells. Therefore, in the future, mutation-dependent neoantigens obtained by appropriate pharmacological intervention appear to disclose a novel approach for enhancing the therapeutic efficacy of ICpI in cancer patients.

Original languageEnglish
Pages (from-to)41641-41669
Number of pages29
JournalOncotarget
Volume8
Issue number25
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Immunotherapy
Triazenes
Dacarbazine
temozolomide
Pharmaceutical Preparations
Mutation
Neoplasms
Chemical Phenomena
Methylnitronitrosoguanidine
Histocompatibility Antigens
Guanine
Mutagenesis
Leukemia
Pharmacology
Oxygen
Equipment and Supplies
Survival
DNA
Therapeutics

Keywords

  • Cancer immunotherapy
  • DNA repair
  • Drug-induced neoantigens
  • Immune checkpoints
  • Triazene compounds

ASJC Scopus subject areas

  • Oncology

Cite this

Franzese, O., Torino, F., Fuggetta, M. P., Aquino, A., Roselli, M., Bonmassar, E., ... D'Atri, S. (2017). Tumor immunotherapy: Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget, 8(25), 41641-41669. https://doi.org/10.18632/oncotarget.16335

Tumor immunotherapy : Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. / Franzese, Ornella; Torino, Francesco; Fuggetta, Maria Pia; Aquino, Angelo; Roselli, Mario; Bonmassar, Enzo; Giuliani, Anna; D'Atri, Stefania.

In: Oncotarget, Vol. 8, No. 25, 01.01.2017, p. 41641-41669.

Research output: Contribution to journalReview article

Franzese, O, Torino, F, Fuggetta, MP, Aquino, A, Roselli, M, Bonmassar, E, Giuliani, A & D'Atri, S 2017, 'Tumor immunotherapy: Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors', Oncotarget, vol. 8, no. 25, pp. 41641-41669. https://doi.org/10.18632/oncotarget.16335
Franzese O, Torino F, Fuggetta MP, Aquino A, Roselli M, Bonmassar E et al. Tumor immunotherapy: Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget. 2017 Jan 1;8(25):41641-41669. https://doi.org/10.18632/oncotarget.16335
Franzese, Ornella ; Torino, Francesco ; Fuggetta, Maria Pia ; Aquino, Angelo ; Roselli, Mario ; Bonmassar, Enzo ; Giuliani, Anna ; D'Atri, Stefania. / Tumor immunotherapy : Drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. In: Oncotarget. 2017 ; Vol. 8, No. 25. pp. 41641-41669.
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