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Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials

BACKGROUND: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tu...

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Autores principales: Ellingsen, Espen Basmo, Aamdal, Elin, Guren, Tormod, Lilleby, Wolfgang, Brunsvig, Paal F, Mangsbo, Sara M, Aamdal, Steinar, Hovig, Eivind, Mensali, Nadia, Gaudernack, Gustav, Inderberg, Else Marit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134181/
https://www.ncbi.nlm.nih.gov/pubmed/35613827
http://dx.doi.org/10.1136/jitc-2021-004345
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author Ellingsen, Espen Basmo
Aamdal, Elin
Guren, Tormod
Lilleby, Wolfgang
Brunsvig, Paal F
Mangsbo, Sara M
Aamdal, Steinar
Hovig, Eivind
Mensali, Nadia
Gaudernack, Gustav
Inderberg, Else Marit
author_facet Ellingsen, Espen Basmo
Aamdal, Elin
Guren, Tormod
Lilleby, Wolfgang
Brunsvig, Paal F
Mangsbo, Sara M
Aamdal, Steinar
Hovig, Eivind
Mensali, Nadia
Gaudernack, Gustav
Inderberg, Else Marit
author_sort Ellingsen, Espen Basmo
collection PubMed
description BACKGROUND: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response. Three phase I/IIa clinical trials covering malignant melanoma, non-small cell lung cancer, and prostate cancer have been completed, with patients in follow-up for up to 8 years. METHODS: 52 patients were enrolled across the three trials. UV1 was given as monotherapy in the lung cancer trial and concurrent with combined androgen blockade in the prostate cancer trial. In the melanoma study, patients initiated ipilimumab treatment 1 week after the first vaccine dose. Patients were followed for UV1-specific immune responses at frequent intervals during vaccination, and every 6 months for up to 8 years in a follow-up period. Phenotypic and functional characterizations were performed on patient-derived vaccine-specific T cell responses. RESULTS: In total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen. CONCLUSION: Long-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer.
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spelling pubmed-91341812022-06-10 Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials Ellingsen, Espen Basmo Aamdal, Elin Guren, Tormod Lilleby, Wolfgang Brunsvig, Paal F Mangsbo, Sara M Aamdal, Steinar Hovig, Eivind Mensali, Nadia Gaudernack, Gustav Inderberg, Else Marit J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response. Three phase I/IIa clinical trials covering malignant melanoma, non-small cell lung cancer, and prostate cancer have been completed, with patients in follow-up for up to 8 years. METHODS: 52 patients were enrolled across the three trials. UV1 was given as monotherapy in the lung cancer trial and concurrent with combined androgen blockade in the prostate cancer trial. In the melanoma study, patients initiated ipilimumab treatment 1 week after the first vaccine dose. Patients were followed for UV1-specific immune responses at frequent intervals during vaccination, and every 6 months for up to 8 years in a follow-up period. Phenotypic and functional characterizations were performed on patient-derived vaccine-specific T cell responses. RESULTS: In total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen. CONCLUSION: Long-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer. BMJ Publishing Group 2022-05-24 /pmc/articles/PMC9134181/ /pubmed/35613827 http://dx.doi.org/10.1136/jitc-2021-004345 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Ellingsen, Espen Basmo
Aamdal, Elin
Guren, Tormod
Lilleby, Wolfgang
Brunsvig, Paal F
Mangsbo, Sara M
Aamdal, Steinar
Hovig, Eivind
Mensali, Nadia
Gaudernack, Gustav
Inderberg, Else Marit
Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title_full Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title_fullStr Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title_full_unstemmed Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title_short Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials
title_sort durable and dynamic htert immune responses following vaccination with the long-peptide cancer vaccine uv1: long-term follow-up of three phase i clinical trials
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134181/
https://www.ncbi.nlm.nih.gov/pubmed/35613827
http://dx.doi.org/10.1136/jitc-2021-004345
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