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

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http://hdl.handle.net/10138/332857

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Peltonen , K , Feola , S , Umer , H M , Chiaro , J , Mermelekas , G , Ylösmaki , E , Pesonen , S , Branca , R M M , Lehtiö , J & Cerullo , V 2021 , ' Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy ' , Cancers , vol. 13 , no. 14 , 3408 . https://doi.org/10.3390/cancers13143408

Title: Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy
Author: Peltonen, Karita; Feola, Sara; Umer, Husen M.; Chiaro, Jacopo; Mermelekas, Georgios; Ylösmaki, Erkko; Pesonen, Sari; Branca, Rui M. M.; Lehtiö, Janne; Cerullo, Vincenzo
Contributor organization: TRIMM - Translational Immunology Research Program
ImmunoViroTherapy Lab
Division of Pharmaceutical Biosciences
Drug Research Program
Digital Precision Cancer Medicine (iCAN)
Date: 2021-07
Language: eng
Number of pages: 17
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers13143408
URI: http://hdl.handle.net/10138/332857
Abstract: Simple Summary Immunotherapy has revolutionized cancer treatment, yet many tumors remain resistant to current immuno-oncology therapies. Here we explore a novel, customized oncolytic adenovirus vaccine platform as immunotherapy in a resistant tumor model. We present a workflow for customizing the oncolytic vaccine for improved tumor targeting. This targeting is based on experimentally discovered tumor antigens, which are incorporated as active components of the vaccine formulation. The pipeline may be further applied for designing personalized therapeutic cancer vaccines. 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.
Subject: tumor antigen
endogenous retrovirus
cancer vaccine
immunotherapy
immunopeptidome
ligandome
breast cancer
mass spectrometry
oncolytic vaccine
T-CELL EXHAUSTION
MASS-SPECTROMETRY
TUMOR
IDENTIFICATION
REPERTOIRE
PD-1
IMMUNOTHERAPY
LYMPHOCYTES
HALLMARKS
SELECTION
317 Pharmacy
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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