Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interro-gating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggres-sive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique anti-gens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexi-ble and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating im-munopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.
Therapeutic cancer vaccination with immunopeptidomics-discovered antigens confers protective antitumor efficacy / Peltonen, K.; Feola, S.; Umer, H. M.; Chiaro, J.; Mermelekas, G.; Ylosmaki, E.; Pesonen, S.; Branca, R. M. M.; Lehtio, J.; Cerullo, V.. - In: CANCERS. - ISSN 2072-6694. - 13:14(2021). [10.3390/cancers13143408]
Therapeutic cancer vaccination with immunopeptidomics-discovered antigens confers protective antitumor efficacy
Feola S.;Cerullo V.
2021
Abstract
Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interro-gating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggres-sive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique anti-gens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexi-ble and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating im-munopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
