Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy.

breast cancer cancer vaccine endogenous retrovirus immunopeptidome immunotherapy ligandome mass spectrometry oncolytic vaccine tumor antigen

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
07 Jul 2021
Historique:
received: 03 06 2021
revised: 01 07 2021
accepted: 02 07 2021
entrez: 24 7 2021
pubmed: 25 7 2021
medline: 25 7 2021
Statut: epublish

Résumé

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 interrogating 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 aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, 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 flexible and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating immunopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.

Identifiants

pubmed: 34298622
pii: cancers13143408
doi: 10.3390/cancers13143408
pmc: PMC8306067
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : H2020 European Research Council
ID : 681219
Organisme : Jane ja Aatos Erkon Säätiö
ID : 4705796
Organisme : HiLIFE Fellow
ID : 797011004
Organisme : Cancer Finnish Foundation
ID : 4706116
Organisme : Magnus Ehrnroothin Säätiö
ID : 4706235
Organisme : Vetenskapsrådet
ID : 2015-04622
Organisme : Stiftelsen för Strategisk Forskning
Organisme : Cancerfonden
Organisme : Barncancerfonden
Organisme : Cancer Research Funds of Radiumhemmet

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Auteurs

Karita Peltonen (K)

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, 00790 Helsinki, Finland.
iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00790 Helsinki, Finland.

Sara Feola (S)

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, 00790 Helsinki, Finland.
iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00790 Helsinki, Finland.

Husen M Umer (HM)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Solna, Sweden.

Jacopo Chiaro (J)

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, 00790 Helsinki, Finland.
iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00790 Helsinki, Finland.

Georgios Mermelekas (G)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Solna, Sweden.

Erkko Ylösmäki (E)

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, 00790 Helsinki, Finland.
iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00790 Helsinki, Finland.

Sari Pesonen (S)

Valo Therapeutics Oy, 00790 Helsinki, Finland.

Rui M M Branca (RMM)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Solna, Sweden.

Janne Lehtiö (J)

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Solna, Sweden.

Vincenzo Cerullo (V)

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), University of Helsinki, 00790 Helsinki, Finland.
iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00790 Helsinki, Finland.

Classifications MeSH