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Clinical efficacy o...
Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor priming in patients with checkpoint inhibitor-resistant metastatic melanoma
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- Borch, Troels Holz (author)
- Herlev Hospital
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- Harbst, Katja (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Rana, Aynal Haque (author)
- Herlev Hospital
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- Andersen, Rikke (author)
- Herlev Hospital
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- Martinenaite, Evelina (author)
- Herlev Hospital
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- Kongsted, Per (author)
- Herlev Hospital
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- Pedersen, Magnus (author)
- Herlev Hospital
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- Nielsen, Morten (author)
- Herlev Hospital
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- Kjeldsen, Julie Westerlin (author)
- Herlev Hospital
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- Kverneland, Anders Handrup (author)
- Herlev Hospital
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- Lauss, Martin (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Hölmich, Lisbet Rosenkrantz (author)
- Herlev Hospital,University of Copenhagen
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- Hendel, Helle (author)
- Herlev Hospital
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- Met, Özcan (author)
- Herlev Hospital,University of Copenhagen
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- Jönsson, Göran (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Donia, Marco (author)
- Herlev Hospital,University of Copenhagen
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- Marie Svane, Inge (author)
- University of Copenhagen,Herlev Hospital
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(creator_code:org_t)
- 2021-07-01
- 2021
- English.
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In: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 9:7
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http://dx.doi.org/10... (free)
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https://jitc.bmj.com...
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https://doi.org/10.1...
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Abstract
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- PURPOSE: Despite impressive response rates following adoptive transfer of autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, improvement is needed to increase the efficacy and broaden the applicability of this treatment. We evaluated the use of vemurafenib, a small-molecule BRAF inhibitor with immunomodulatory properties, as priming before TIL harvest and adoptive T cell therapy in a phase I/II clinical trial. METHODS: 12 patients were treated with vemurafenib for 7 days before tumor excision and during the following weeks until TIL infusion. TILs were grown from tumor fragments, expanded in vitro and reinfused to the patient preceded by a lymphodepleting chemotherapy regimen and followed by interleukin-2 infusion. Extensive immune monitoring, tumor profiling and T cell receptor sequencing were performed. RESULTS: No unexpected toxicity was observed, and treatment was well tolerated. Of 12 patients, 1 achieved a complete response, 8 achieved partial response and 3 achieved stable disease. A PR and the CR are ongoing for 23 and 43 months, respectively. In vitro anti-tumor reactivity was found in TILs from 10 patients, including all patients achieving objective response. Serum and tumor biomarker analyses indicate that baseline cytokine levels and the number of T cell clones may predict response to TIL therapy. Further, TCR sequencing suggested skewing of TCR repertoire during in vitro expansion, promoting certain low frequency clonotypes. CONCLUSIONS: Priming with vemurafenib before infusion of TILs was safe and feasible, and induced objective clinical responses in this cohort of patients with checkpoint inhibitor-resistant metastatic melanoma. In this trial, vemurafenib treatment seemed to decrease attrition and could be considered to bridge the waiting time while TILs are prepared.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- adoptive
- clinical trials as topic
- immunotherapy
- lymphocytes
- melanoma
- tumor-infiltrating
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Borch, Troels Ho ...
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Harbst, Katja
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Rana, Aynal Haqu ...
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Andersen, Rikke
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Martinenaite, Ev ...
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Kongsted, Per
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Pedersen, Magnus
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Nielsen, Morten
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Kjeldsen, Julie ...
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Kverneland, Ande ...
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Lauss, Martin
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Hölmich, Lisbet ...
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Hendel, Helle
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Met, Özcan
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Jönsson, Göran
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Donia, Marco
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Marie Svane, Ing ...
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