A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
- University of Helsinki, Finland
- University Vita e Salute San Raffaele, Italy
- University of Helsinki, Finland
- Valo Therapeutics Oy, Finland
- Karolinska Institutet, Sweden
- Karolinska Institute, Sweden
Abstract
Beside the isolation and identification of MHC-I restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective anti-tumor 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 anti-tumor 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 the HEX software. The latter is a tool previously developed by Chiaro et al. (1), 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 (twenty-six in total) was further tested in a functional characterization assay using interferon-g ELISpot (Enzyme-Linked Immunospot), 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, non-treated, 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.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026463. The ligandome dataset is currently hidden but will be made public upon eventual acceptance of the current manuscript.Reviewer Account details for ligandome data accessing: https://www.ebi.ac.uk/pride/login PXD026463Username: reviewer_pxd026463@ebi.ac.ukPassword: oMUWIAw3
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Noncoding regions are the main source of targetable tumor-specific antigensNCBI Gene Expression Omnibus, GSE111092.
Article and author information
Author details
Michaela Feodoroff
Funding
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were reviewed and approved by the Experimental Animal Committee of the University of Helsinki and the Provincial Government of Southern Finland (license number ESAVI/11895/2019).4-6 weeks old female Balb/cOlaHsd mice were obtained from Envigo (Laboratory, Bar Harbor, Maine UK).
Copyright
© 2022, Feola et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines
eLife 11:e71156.
https://doi.org/10.7554/eLife.71156
Further reading
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Background: Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.
Methods: To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.
Results: We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.
Conclusion: Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.
Funding: Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).
