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Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma
The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing of tumor samples and artificial intelligence (AI) allow fa...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757480/ https://www.ncbi.nlm.nih.gov/pubmed/35036074 http://dx.doi.org/10.1080/2162402X.2021.2023255 |
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author | Mørk, Sofie Kirial Kadivar, Mohammad Bol, Kalijn Fredrike Draghi, Arianna Westergaard, Marie Christine Wulff Skadborg, Signe Koggersbøl Overgaard, Nana Sørensen, Anders Bundgård Rasmussen, Ida Svahn Andreasen, Lars Vibe Yde, Christina Westmose Trolle, Thomas Garde, Christian Friis-Nielsen, Jens Nørgaard, Nis Christensen, Dennis Kringelum, Jens Vindahl Donia, Marco Hadrup, Sine Reker Svane, Inge Marie |
author_facet | Mørk, Sofie Kirial Kadivar, Mohammad Bol, Kalijn Fredrike Draghi, Arianna Westergaard, Marie Christine Wulff Skadborg, Signe Koggersbøl Overgaard, Nana Sørensen, Anders Bundgård Rasmussen, Ida Svahn Andreasen, Lars Vibe Yde, Christina Westmose Trolle, Thomas Garde, Christian Friis-Nielsen, Jens Nørgaard, Nis Christensen, Dennis Kringelum, Jens Vindahl Donia, Marco Hadrup, Sine Reker Svane, Inge Marie |
author_sort | Mørk, Sofie Kirial |
collection | PubMed |
description | The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing of tumor samples and artificial intelligence (AI) allow fast and systematic prediction of tumor neoantigens. This study investigates feasibility, safety, immunity, and anti-tumor potential of the personalized peptide-based neoantigen vaccine, EVX-01, including the novel CD8(+) T-cell inducing adjuvant, CAF®09b, in patients with metastatic melanoma (NTC03715985). The AI platform PIONEER(TM) was used for identification of tumor-derived neoantigens to be included in a peptide-based personalized therapeutic cancer vaccine. EVX-01 immunotherapy consisted of 6 administrations with 5–10 PIONEER(TM)-predicted neoantigens as synthetic peptides combined with the novel liposome-based Cationic Adjuvant Formulation 09b (CAF®09b) to strengthen T-cell responses. EVX-01 was combined with immune checkpoint inhibitors to augment the activity of EVX-01-induced immune responses. The primary endpoint was safety, exploratory endpoints included feasibility, immunologic and objective responses. This interim analysis reports the results from the first dose-level cohort of five patients. We documented a short vaccine manufacturing time of 48–55 days which enabled the initiation of EVX-01 treatment within 60 days from baseline biopsy. No severe adverse events were observed. EVX-01 elicited long-lasting EVX-01-specific T-cell responses in all patients. Competitive manufacturing time was demonstrated. EVX-01 was shown to be safe and able to elicit immune responses targeting tumor neoantigens with encouraging early indications of a clinical and meaningful antitumor efficacy, warranting further study. |
format | Online Article Text |
id | pubmed-8757480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-87574802022-01-14 Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma Mørk, Sofie Kirial Kadivar, Mohammad Bol, Kalijn Fredrike Draghi, Arianna Westergaard, Marie Christine Wulff Skadborg, Signe Koggersbøl Overgaard, Nana Sørensen, Anders Bundgård Rasmussen, Ida Svahn Andreasen, Lars Vibe Yde, Christina Westmose Trolle, Thomas Garde, Christian Friis-Nielsen, Jens Nørgaard, Nis Christensen, Dennis Kringelum, Jens Vindahl Donia, Marco Hadrup, Sine Reker Svane, Inge Marie Oncoimmunology Research Article The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing of tumor samples and artificial intelligence (AI) allow fast and systematic prediction of tumor neoantigens. This study investigates feasibility, safety, immunity, and anti-tumor potential of the personalized peptide-based neoantigen vaccine, EVX-01, including the novel CD8(+) T-cell inducing adjuvant, CAF®09b, in patients with metastatic melanoma (NTC03715985). The AI platform PIONEER(TM) was used for identification of tumor-derived neoantigens to be included in a peptide-based personalized therapeutic cancer vaccine. EVX-01 immunotherapy consisted of 6 administrations with 5–10 PIONEER(TM)-predicted neoantigens as synthetic peptides combined with the novel liposome-based Cationic Adjuvant Formulation 09b (CAF®09b) to strengthen T-cell responses. EVX-01 was combined with immune checkpoint inhibitors to augment the activity of EVX-01-induced immune responses. The primary endpoint was safety, exploratory endpoints included feasibility, immunologic and objective responses. This interim analysis reports the results from the first dose-level cohort of five patients. We documented a short vaccine manufacturing time of 48–55 days which enabled the initiation of EVX-01 treatment within 60 days from baseline biopsy. No severe adverse events were observed. EVX-01 elicited long-lasting EVX-01-specific T-cell responses in all patients. Competitive manufacturing time was demonstrated. EVX-01 was shown to be safe and able to elicit immune responses targeting tumor neoantigens with encouraging early indications of a clinical and meaningful antitumor efficacy, warranting further study. Taylor & Francis 2022-01-10 /pmc/articles/PMC8757480/ /pubmed/35036074 http://dx.doi.org/10.1080/2162402X.2021.2023255 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Mørk, Sofie Kirial Kadivar, Mohammad Bol, Kalijn Fredrike Draghi, Arianna Westergaard, Marie Christine Wulff Skadborg, Signe Koggersbøl Overgaard, Nana Sørensen, Anders Bundgård Rasmussen, Ida Svahn Andreasen, Lars Vibe Yde, Christina Westmose Trolle, Thomas Garde, Christian Friis-Nielsen, Jens Nørgaard, Nis Christensen, Dennis Kringelum, Jens Vindahl Donia, Marco Hadrup, Sine Reker Svane, Inge Marie Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title | Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title_full | Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title_fullStr | Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title_full_unstemmed | Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title_short | Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma |
title_sort | personalized therapy with peptide-based neoantigen vaccine (evx-01) including a novel adjuvant, caf®09b, in patients with metastatic melanoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757480/ https://www.ncbi.nlm.nih.gov/pubmed/35036074 http://dx.doi.org/10.1080/2162402X.2021.2023255 |
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