Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine
<p dir="ltr">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...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , , , , , |
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2019
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إضافة وسم
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| _version_ | 1864513523077349376 |
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| author | Mona O. Mohsen (4056964) |
| author2 | Monique Vogel (405685) Carsten Riether (509910) Julius Muller (4098391) Silvia Salatino (184189) Nicola Ternette (68528) Ariane C. Gomes (7116413) Gustavo Cabral-Miranda (6641204) Aadil El-Turabi (4348864) Christiane Ruedl (211913) Thomas M. Kundig (18131773) Said Dermime (79420) Alexander Knuth (11104) Daniel E. Speiser (8262588) Martin F. Bachmann (7116422) |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Mona O. Mohsen (4056964) Monique Vogel (405685) Carsten Riether (509910) Julius Muller (4098391) Silvia Salatino (184189) Nicola Ternette (68528) Ariane C. Gomes (7116413) Gustavo Cabral-Miranda (6641204) Aadil El-Turabi (4348864) Christiane Ruedl (211913) Thomas M. Kundig (18131773) Said Dermime (79420) Alexander Knuth (11104) Daniel E. Speiser (8262588) Martin F. Bachmann (7116422) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mona O. Mohsen (4056964) Monique Vogel (405685) Carsten Riether (509910) Julius Muller (4098391) Silvia Salatino (184189) Nicola Ternette (68528) Ariane C. Gomes (7116413) Gustavo Cabral-Miranda (6641204) Aadil El-Turabi (4348864) Christiane Ruedl (211913) Thomas M. Kundig (18131773) Said Dermime (79420) Alexander Knuth (11104) Daniel E. Speiser (8262588) Martin F. Bachmann (7116422) |
| dc.date.none.fl_str_mv | 2019-05-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2019.01015 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Targeting_Mutated_Plus_Germline_Epitopes_Confers_Pre-clinical_Efficacy_of_an_Instantly_Formulated_Cancer_Nano-Vaccine/25376479 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology virus-like particles vaccine personalized melanoma neoantigen mutated germline |
| dc.title.none.fl_str_mv | Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2019.01015" target="_blank">https://dx.doi.org/10.3389/fimmu.2019.01015</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_f9c3560b88cc12908fddbf394c73edd0 |
| identifier_str_mv | 10.3389/fimmu.2019.01015 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25376479 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-VaccineMona O. Mohsen (4056964)Monique Vogel (405685)Carsten Riether (509910)Julius Muller (4098391)Silvia Salatino (184189)Nicola Ternette (68528)Ariane C. Gomes (7116413)Gustavo Cabral-Miranda (6641204)Aadil El-Turabi (4348864)Christiane Ruedl (211913)Thomas M. Kundig (18131773)Said Dermime (79420)Alexander Knuth (11104)Daniel E. Speiser (8262588)Martin F. Bachmann (7116422)Biomedical and clinical sciencesImmunologyvirus-like particlesvaccinepersonalizedmelanomaneoantigenmutatedgermline<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2019.01015" target="_blank">https://dx.doi.org/10.3389/fimmu.2019.01015</a></p>2019-05-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2019.01015https://figshare.com/articles/journal_contribution/Targeting_Mutated_Plus_Germline_Epitopes_Confers_Pre-clinical_Efficacy_of_an_Instantly_Formulated_Cancer_Nano-Vaccine/25376479CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/253764792019-05-15T03:00:00Z |
| spellingShingle | Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine Mona O. Mohsen (4056964) Biomedical and clinical sciences Immunology virus-like particles vaccine personalized melanoma neoantigen mutated germline |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Biomedical and clinical sciences Immunology virus-like particles vaccine personalized melanoma neoantigen mutated germline |