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Engineering editopes through programmable RNA editing toward tumor neoantigen generation: method

Neoepitope-based therapies hold great promise for cancer immunotherapy because they target tumor-specific mutations and elicit potent anti-tumor T-cell responses. However, their clinical implementation remains limited by the complexity of neoepitope discovery and uncertainty regarding presentation b...

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Main Authors: Pecori, Riccardo (Author) , Casati, Beatrice (Author) , Merdler-Rabinowicz, Rona (Author) , Landesman, Netanel (Author) , Sanghvi, Khwab (Author) , Zens, Stefan (Author) , Bilgin, Ece (Author) , Topouzi, Mantiana (Author) , Kipfstuhl, Kai (Author) , Pinamonti, Veronica (Author) , Arnold, Annette (Author) , Abukhalaf, Mohammad (Author) , Gomez-Zepeda, David (Author) , Tenzer, Stefan (Author) , Lindner, John M. (Author) , Platten, Michael (Author) , Offringa, Rienk (Author) , Carretero, Rafael (Author) , Ruppin, Eytan (Author) , Levanon, Erez Y. (Author) , Papavasiliou, Nina (Author)
Format: Article (Journal)
Language:English
Published: 2026
In: The EMBO journal
Year: 2026, Pages: 1-24
ISSN:1460-2075
DOI:10.1038/s44318-026-00870-5
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44318-026-00870-5
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Author Notes:Riccardo Pecori, Beatrice Casati, Rona Merdler-Rabinowicz, Netanel Landesman, Khwab Sanghvi, Stefan Zens, Ece Bilgin, Mantiana Topouzi, Kai Kipfstuhl, Veronica Pinamonti, Annette Arnold, Mohammad Abukhalaf, David Gomez-Zepeda, Stefan Tenzer, John M. Lindner, Michael Platten, Rienk Offringa, Rafael Carretero, Eytan Ruppin, Erez Y. Levanon & Fotini Nina Papavasiliou
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Summary:Neoepitope-based therapies hold great promise for cancer immunotherapy because they target tumor-specific mutations and elicit potent anti-tumor T-cell responses. However, their clinical implementation remains limited by the complexity of neoepitope discovery and uncertainty regarding presentation by tumor cells. A potential alternative is the generation of immunogenic neoepitopes directly within cancer cells through programmable RNA editing. Here, we develop Short Precise-Encodable ADAR Recruiting (SPEAR) gRNAs that harness endogenous ADAR1 to direct precise adenosine-to-inosine (A-to-I) editing at selected transcript sites. Using these gRNAs, we demonstrate the generation of immunogenic neoepitopes through RNA editing at the transcript level, termed editopes. In a proof-of-concept model based on the melanoma antigen MART-1, SPEAR-mediated RNA editing restored antigen-specific T cell recognition and enabled tumor control in vivo. Finally, we developed a computational pipeline to identify candidate tumor-selective neoepitopes across multiple cancer types amenable to guided RNA editing. Our findings establish programmable RNA editing as a strategy for engineering immunogenic editopes and provide a framework for neoepitope-directed cancer immunotherapy.
Item Description:Online veröffentlicht: 14. August 2026, Artikelversion: 14. August 2026
Gesehen am 01.09.2026
Physical Description:Online Resource
ISSN:1460-2075
DOI:10.1038/s44318-026-00870-5

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