Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine

Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are...

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Main Authors: Mohsen, Mona O., Vogel, Monique, Riether, Carsten, Muller, Julius, Salatino, Silvia, Ternette, Nicola, Gomes, Ariane C., Cabral-Miranda, Gustavo, El-Turabi, Aadil, Ruedl, Christiane, Kundig, Thomas M., Dermime, Said, Knuth, Alexander, Speiser, Daniel E., Bachmann, Martin F.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/104713
http://hdl.handle.net/10220/48630
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1047132023-02-28T17:04:19Z Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine Mohsen, Mona O. Vogel, Monique Riether, Carsten Muller, Julius Salatino, Silvia Ternette, Nicola Gomes, Ariane C. Cabral-Miranda, Gustavo El-Turabi, Aadil Ruedl, Christiane Kundig, Thomas M. Dermime, Said Knuth, Alexander Speiser, Daniel E. Bachmann, Martin F. School of Biological Sciences Molecular Genetics and Cell Biology Virus-like Particles Vaccine DRNTU::Science::Biological sciences Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation. Published version 2019-06-11T04:47:28Z 2019-12-06T21:38:04Z 2019-06-11T04:47:28Z 2019-12-06T21:38:04Z 2019 Journal Article Mohsen, M. O., Vogel, M., Riether, C., Muller, J., Salatino, S., Ternette, N., . . . Bachmann, M. F. (2019). Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine. Frontiers in Immunology, 10, 1015-. doi:10.3389/fimmu.2019.01015 https://hdl.handle.net/10356/104713 http://hdl.handle.net/10220/48630 10.3389/fimmu.2019.01015 en Frontiers in Immunology © 2019 Mohsen, Vogel, Riether, Muller, Salatino, Ternette, Gomes, Cabral-Miranda, El-Turabi, Ruedl, Kundig, Dermime, Knuth, Speiser and Bachmann. 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. 14 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Virus-like Particles
Vaccine
DRNTU::Science::Biological sciences
spellingShingle Virus-like Particles
Vaccine
DRNTU::Science::Biological sciences
Mohsen, Mona O.
Vogel, Monique
Riether, Carsten
Muller, Julius
Salatino, Silvia
Ternette, Nicola
Gomes, Ariane C.
Cabral-Miranda, Gustavo
El-Turabi, Aadil
Ruedl, Christiane
Kundig, Thomas M.
Dermime, Said
Knuth, Alexander
Speiser, Daniel E.
Bachmann, Martin F.
Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
description Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Mohsen, Mona O.
Vogel, Monique
Riether, Carsten
Muller, Julius
Salatino, Silvia
Ternette, Nicola
Gomes, Ariane C.
Cabral-Miranda, Gustavo
El-Turabi, Aadil
Ruedl, Christiane
Kundig, Thomas M.
Dermime, Said
Knuth, Alexander
Speiser, Daniel E.
Bachmann, Martin F.
format Article
author Mohsen, Mona O.
Vogel, Monique
Riether, Carsten
Muller, Julius
Salatino, Silvia
Ternette, Nicola
Gomes, Ariane C.
Cabral-Miranda, Gustavo
El-Turabi, Aadil
Ruedl, Christiane
Kundig, Thomas M.
Dermime, Said
Knuth, Alexander
Speiser, Daniel E.
Bachmann, Martin F.
author_sort Mohsen, Mona O.
title Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
title_short Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
title_full Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
title_fullStr Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
title_full_unstemmed Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
title_sort targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
publishDate 2019
url https://hdl.handle.net/10356/104713
http://hdl.handle.net/10220/48630
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