Cargando…
Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine
INTRODUCTION: Tumor-specific mutations generate neoepitopes unique to the cancer that can be recognized by the immune system, making them appealing targets for therapeutic cancer vaccines. Since the vast majority of tumor mutations are patient-specific, it is crucial for cancer vaccine designs to be...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499626/ https://www.ncbi.nlm.nih.gov/pubmed/37720215 http://dx.doi.org/10.3389/fimmu.2023.1234912 |
_version_ | 1785105750388899840 |
---|---|
author | Barrio-Calvo, Marina Kofoed, Søren Vester Holste, Sofie Cens Sørensen, Anders Bundgård Viborg, Nadia Kringelum, Jens Vindahl Kleine-Kohlbrecher, Daniela Steenmans, Christian Skjødt Thygesen, Christian Bahne Rønø, Birgitte Friis, Stine |
author_facet | Barrio-Calvo, Marina Kofoed, Søren Vester Holste, Sofie Cens Sørensen, Anders Bundgård Viborg, Nadia Kringelum, Jens Vindahl Kleine-Kohlbrecher, Daniela Steenmans, Christian Skjødt Thygesen, Christian Bahne Rønø, Birgitte Friis, Stine |
author_sort | Barrio-Calvo, Marina |
collection | PubMed |
description | INTRODUCTION: Tumor-specific mutations generate neoepitopes unique to the cancer that can be recognized by the immune system, making them appealing targets for therapeutic cancer vaccines. Since the vast majority of tumor mutations are patient-specific, it is crucial for cancer vaccine designs to be compatible with individualized treatment strategies. Plasmid DNA vaccines have substantiated the immunogenicity and tumor eradication capacity of cancer neoepitopes in preclinical models. Moreover, early clinical trials evaluating personalized neoepitope vaccines have indicated favorable safety profiles and demonstrated their ability to elicit specific immune responses toward the vaccine neoepitopes. METHODS: By fusing in silico predicted neoepitopes to molecules with affinity for receptors on the surface of APCs, such as chemokine (C-C motif) ligand 19 (CCL19), we designed an APC-targeting cancer vaccine and evaluated their ability to induce T-cell responses and anti-tumor efficacy in the BALB/c syngeneic preclinical tumor model. RESULTS: In this study, we demonstrate how the addition of an antigen-presenting cell (APC) binding molecule to DNA-encoded cancer neoepitopes improves neoepitope-specific T-cell responses and the anti-tumor efficacy of plasmid DNA vaccines. Dose-response evaluation and longitudinal analysis of neoepitope-specific T-cell responses indicate that combining APC-binding molecules with the delivery of personalized tumor antigens holds the potential to improve the clinical efficacy of therapeutic DNA cancer vaccines. DISCUSSION: Our findings indicate the potential of the APC-targeting strategy to enhance personalized DNA cancer vaccines while acknowledging the need for further research to investigate its molecular mechanism of action and to translate the preclinical results into effective treatments for cancer patients. |
format | Online Article Text |
id | pubmed-10499626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104996262023-09-15 Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine Barrio-Calvo, Marina Kofoed, Søren Vester Holste, Sofie Cens Sørensen, Anders Bundgård Viborg, Nadia Kringelum, Jens Vindahl Kleine-Kohlbrecher, Daniela Steenmans, Christian Skjødt Thygesen, Christian Bahne Rønø, Birgitte Friis, Stine Front Immunol Immunology INTRODUCTION: Tumor-specific mutations generate neoepitopes unique to the cancer that can be recognized by the immune system, making them appealing targets for therapeutic cancer vaccines. Since the vast majority of tumor mutations are patient-specific, it is crucial for cancer vaccine designs to be compatible with individualized treatment strategies. Plasmid DNA vaccines have substantiated the immunogenicity and tumor eradication capacity of cancer neoepitopes in preclinical models. Moreover, early clinical trials evaluating personalized neoepitope vaccines have indicated favorable safety profiles and demonstrated their ability to elicit specific immune responses toward the vaccine neoepitopes. METHODS: By fusing in silico predicted neoepitopes to molecules with affinity for receptors on the surface of APCs, such as chemokine (C-C motif) ligand 19 (CCL19), we designed an APC-targeting cancer vaccine and evaluated their ability to induce T-cell responses and anti-tumor efficacy in the BALB/c syngeneic preclinical tumor model. RESULTS: In this study, we demonstrate how the addition of an antigen-presenting cell (APC) binding molecule to DNA-encoded cancer neoepitopes improves neoepitope-specific T-cell responses and the anti-tumor efficacy of plasmid DNA vaccines. Dose-response evaluation and longitudinal analysis of neoepitope-specific T-cell responses indicate that combining APC-binding molecules with the delivery of personalized tumor antigens holds the potential to improve the clinical efficacy of therapeutic DNA cancer vaccines. DISCUSSION: Our findings indicate the potential of the APC-targeting strategy to enhance personalized DNA cancer vaccines while acknowledging the need for further research to investigate its molecular mechanism of action and to translate the preclinical results into effective treatments for cancer patients. Frontiers Media S.A. 2023-08-29 /pmc/articles/PMC10499626/ /pubmed/37720215 http://dx.doi.org/10.3389/fimmu.2023.1234912 Text en Copyright © 2023 Barrio-Calvo, Kofoed, Holste, Sørensen, Viborg, Kringelum, Kleine-Kohlbrecher, Steenmans, Thygesen, Rønø and Friis https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Barrio-Calvo, Marina Kofoed, Søren Vester Holste, Sofie Cens Sørensen, Anders Bundgård Viborg, Nadia Kringelum, Jens Vindahl Kleine-Kohlbrecher, Daniela Steenmans, Christian Skjødt Thygesen, Christian Bahne Rønø, Birgitte Friis, Stine Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title | Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title_full | Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title_fullStr | Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title_full_unstemmed | Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title_short | Targeting neoantigens to APC-surface molecules improves the immunogenicity and anti-tumor efficacy of a DNA cancer vaccine |
title_sort | targeting neoantigens to apc-surface molecules improves the immunogenicity and anti-tumor efficacy of a dna cancer vaccine |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499626/ https://www.ncbi.nlm.nih.gov/pubmed/37720215 http://dx.doi.org/10.3389/fimmu.2023.1234912 |
work_keys_str_mv | AT barriocalvomarina targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT kofoedsørenvester targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT holstesofiecens targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT sørensenandersbundgard targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT viborgnadia targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT kringelumjensvindahl targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT kleinekohlbrecherdaniela targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT steenmanschristianskjødt targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT thygesenchristianbahne targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT rønøbirgitte targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine AT friisstine targetingneoantigenstoapcsurfacemoleculesimprovestheimmunogenicityandantitumorefficacyofadnacancervaccine |