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Characterization of...
Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination
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- Ellingsen, Espen Basmo (författare)
- Norwegian Radium Hosp, Dept Tumor Biol, Inst Canc Res, Oslo, Norway.;Univ Oslo, Fac Med, Oslo, Norway.;Ultimovacs ASA, Oslo, Norway.
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- Bounova, Gergana (författare)
- ENPICOM BV, Da S Hertogenbosch, Netherlands.
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- Kerzeli, Iliana Kyriaki (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci
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- Anzar, Irantzu (författare)
- NEC Oncoimmun, Oslo, Norway.
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- Simnica, Donjete (författare)
- Univ Klinikum Halle Saale, Dept Internal Med Hematol & Oncol 4, Halle, Germany.
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- Aamdal, Elin (författare)
- Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
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- Guren, Tormod (författare)
- Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
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- Clancy, Trevor (författare)
- NEC Oncoimmun, Oslo, Norway.
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- Mezheyeuski, Artur (författare)
- HistoOne AB, Uppsala, Sweden.
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- Inderberg, Else Marit (författare)
- Oslo Univ Hosp, Dept Cellular Therapy, Oslo, Norway.
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- Mangsbo, Sara, 1981- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci,Ultimovacs AB, Uppsala, Sweden.
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- Binder, Mascha (författare)
- Univ Klinikum Halle Saale, Dept Internal Med Hematol & Oncol 4, Halle, Germany.
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- Hovig, Eivind (författare)
- Norwegian Radium Hosp, Dept Tumor Biol, Inst Canc Res, Oslo, Norway.;Univ Oslo, Ctr Bioinformat, Oslo, Norway.
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- Gaudernack, Gustav (författare)
- Ultimovacs ASA, Oslo, Norway.
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Norwegian Radium Hosp, Dept Tumor Biol, Inst Canc Res, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway.;Ultimovacs ASA, Oslo, Norway. ENPICOM BV, Da S Hertogenbosch, Netherlands. (creator_code:org_t)
- 2022-09-11
- 2022
- Engelska.
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Ingår i: Journal of Translational Medicine. - : Springer Nature. - 1479-5876. ; 20
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment.Methods: The trial was an open-label, single-center phase I/11a study. Eligible patients had unresectable metastatic melanoma. Patients received up to 9 UV1 vaccinations and four ipilimumab infusions. Clinical responses were assessed according to RECIST 1.1. Patients were followed up for progression-free survival (PFS) and overall survival (OS). Whole-exome and RNA sequencing, and multiplex immunofluorescence were performed on the biopsies. T cell receptor (TCR) sequencing was performed on the peripheral blood and tumor tissues.Results: Twelve patients were enrolled in the study. Vaccine-specific immune responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-gamma gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-gamma gene signature was detected in clinically responding patients.Conclusion: Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Cancer
- Immunotherapy
- Therapeutic Cancer Vaccine
- Telomerase
- hTERT
- Melanoma
- Ipilimumab
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Ellingsen, Espen ...
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Bounova, Gergana
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Kerzeli, Iliana ...
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Anzar, Irantzu
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Simnica, Donjete
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Aamdal, Elin
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Guren, Tormod
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Clancy, Trevor
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Mezheyeuski, Art ...
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Inderberg, Else ...
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Mangsbo, Sara, 1 ...
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Binder, Mascha
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Hovig, Eivind
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Gaudernack, Gust ...
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