DNA based neoepitope vaccination induces tumor control in syngeneic mouse models

Abstract Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work,...

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Main Authors: Nadia Viborg, Michail Angelos Pavlidis, Marina Barrio-Calvo, Stine Friis, Thomas Trolle, Anders Bundgaard Sørensen, Christian Bahne Thygesen, Søren Vester Kofoed, Daniela Kleine-Kohlbrecher, Sine Reker Hadrup, Birgitte Rønø
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-023-00671-5
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author Nadia Viborg
Michail Angelos Pavlidis
Marina Barrio-Calvo
Stine Friis
Thomas Trolle
Anders Bundgaard Sørensen
Christian Bahne Thygesen
Søren Vester Kofoed
Daniela Kleine-Kohlbrecher
Sine Reker Hadrup
Birgitte Rønø
author_facet Nadia Viborg
Michail Angelos Pavlidis
Marina Barrio-Calvo
Stine Friis
Thomas Trolle
Anders Bundgaard Sørensen
Christian Bahne Thygesen
Søren Vester Kofoed
Daniela Kleine-Kohlbrecher
Sine Reker Hadrup
Birgitte Rønø
author_sort Nadia Viborg
collection DOAJ
description Abstract Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed the ability of plasmid DNA to confer neoepitope immunogenicity and anti-tumor effect in two murine syngeneic cancer models. We demonstrated that neoepitope DNA vaccination led to anti-tumor immunity in the CT26 and B16F10 tumor models, with the long-lasting presence of neoepitope-specific T-cell responses in blood, spleen, and tumors after immunization. We further observed that engagement of both the CD4+ and CD8+ T cell compartments was essential to hamper tumor growth. Additionally, combination therapy with immune checkpoint inhibition provided an additive effect, superior to either monotherapy. DNA vaccination offers a versatile platform that allows the encoding of multiple neoepitopes in a single formulation and is thus a feasible strategy for personalized immunotherapy via neoepitope vaccination.
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spelling doaj.art-018569528672479ca528c27630e5b5be2023-12-02T18:01:26ZengNature Portfolionpj Vaccines2059-01052023-05-018111610.1038/s41541-023-00671-5DNA based neoepitope vaccination induces tumor control in syngeneic mouse modelsNadia Viborg0Michail Angelos Pavlidis1Marina Barrio-Calvo2Stine Friis3Thomas Trolle4Anders Bundgaard Sørensen5Christian Bahne Thygesen6Søren Vester Kofoed7Daniela Kleine-Kohlbrecher8Sine Reker Hadrup9Birgitte Rønø10Evaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechEvaxion BiotechDepartment of Health Technology, Technical University of DenmarkEvaxion BiotechAbstract Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver neoepitopes via various vaccine formulations have demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed the ability of plasmid DNA to confer neoepitope immunogenicity and anti-tumor effect in two murine syngeneic cancer models. We demonstrated that neoepitope DNA vaccination led to anti-tumor immunity in the CT26 and B16F10 tumor models, with the long-lasting presence of neoepitope-specific T-cell responses in blood, spleen, and tumors after immunization. We further observed that engagement of both the CD4+ and CD8+ T cell compartments was essential to hamper tumor growth. Additionally, combination therapy with immune checkpoint inhibition provided an additive effect, superior to either monotherapy. DNA vaccination offers a versatile platform that allows the encoding of multiple neoepitopes in a single formulation and is thus a feasible strategy for personalized immunotherapy via neoepitope vaccination.https://doi.org/10.1038/s41541-023-00671-5
spellingShingle Nadia Viborg
Michail Angelos Pavlidis
Marina Barrio-Calvo
Stine Friis
Thomas Trolle
Anders Bundgaard Sørensen
Christian Bahne Thygesen
Søren Vester Kofoed
Daniela Kleine-Kohlbrecher
Sine Reker Hadrup
Birgitte Rønø
DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
npj Vaccines
title DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
title_full DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
title_fullStr DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
title_full_unstemmed DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
title_short DNA based neoepitope vaccination induces tumor control in syngeneic mouse models
title_sort dna based neoepitope vaccination induces tumor control in syngeneic mouse models
url https://doi.org/10.1038/s41541-023-00671-5
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