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Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine

Mohsen, MO; Vogel, M; Riether, C; Muller, J; Salatinos, S; Ternette, N; Gomes, AC; ... Bachmann, MF; + view all (2019) Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine. Frontiers in Immunology , 10 , Article 1015. 10.3389/fimmu.2019.01015. Green open access

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Abstract

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.

Type: Article
Title: Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2019.01015
Publisher version: https://doi.org/10.3389/fimmu.2019.01015
Language: English
Additional information: Copyright © 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) (http://creativecommons.org/licenses/by/4.0/). 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.
Keywords: virus-like particles, vaccine, personalized, melanoma, neoantigen, mutated, germline
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10082267
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