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A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid...

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Autores principales: Feola, Sara, Chiaro, Jacopo, Martins, Beatriz, Russo, Salvatore, Fusciello, Manlio, Ylösmäki, Erkko, Bonini, Chiara, Ruggiero, Eliana, Hamdan, Firas, Feodoroff, Michaela, Antignani, Gabriella, Viitala, Tapani, Pesonen, Sari, Grönholm, Mikaela, Branca, Rui MM, Lehtiö, Janne, Cerullo, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989416/
https://www.ncbi.nlm.nih.gov/pubmed/35314027
http://dx.doi.org/10.7554/eLife.71156
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author Feola, Sara
Chiaro, Jacopo
Martins, Beatriz
Russo, Salvatore
Fusciello, Manlio
Ylösmäki, Erkko
Bonini, Chiara
Ruggiero, Eliana
Hamdan, Firas
Feodoroff, Michaela
Antignani, Gabriella
Viitala, Tapani
Pesonen, Sari
Grönholm, Mikaela
Branca, Rui MM
Lehtiö, Janne
Cerullo, Vincenzo
author_facet Feola, Sara
Chiaro, Jacopo
Martins, Beatriz
Russo, Salvatore
Fusciello, Manlio
Ylösmäki, Erkko
Bonini, Chiara
Ruggiero, Eliana
Hamdan, Firas
Feodoroff, Michaela
Antignani, Gabriella
Viitala, Tapani
Pesonen, Sari
Grönholm, Mikaela
Branca, Rui MM
Lehtiö, Janne
Cerullo, Vincenzo
author_sort Feola, Sara
collection PubMed
description Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate >8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software. The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. The generated list of candidates (26 in total) was further tested in a functional characterization assay using interferon-γ enzyme-linked immunospot (ELISpot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, nontreated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach.
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spelling pubmed-89894162022-04-08 A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines Feola, Sara Chiaro, Jacopo Martins, Beatriz Russo, Salvatore Fusciello, Manlio Ylösmäki, Erkko Bonini, Chiara Ruggiero, Eliana Hamdan, Firas Feodoroff, Michaela Antignani, Gabriella Viitala, Tapani Pesonen, Sari Grönholm, Mikaela Branca, Rui MM Lehtiö, Janne Cerullo, Vincenzo eLife Medicine Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate >8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software. The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. The generated list of candidates (26 in total) was further tested in a functional characterization assay using interferon-γ enzyme-linked immunospot (ELISpot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, nontreated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach. eLife Sciences Publications, Ltd 2022-03-22 /pmc/articles/PMC8989416/ /pubmed/35314027 http://dx.doi.org/10.7554/eLife.71156 Text en © 2022, Feola et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Feola, Sara
Chiaro, Jacopo
Martins, Beatriz
Russo, Salvatore
Fusciello, Manlio
Ylösmäki, Erkko
Bonini, Chiara
Ruggiero, Eliana
Hamdan, Firas
Feodoroff, Michaela
Antignani, Gabriella
Viitala, Tapani
Pesonen, Sari
Grönholm, Mikaela
Branca, Rui MM
Lehtiö, Janne
Cerullo, Vincenzo
A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title_full A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title_fullStr A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title_full_unstemmed A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title_short A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
title_sort novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989416/
https://www.ncbi.nlm.nih.gov/pubmed/35314027
http://dx.doi.org/10.7554/eLife.71156
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