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Sökning: WFRF:(Martinenaite Evelina) > (2021) > Clinical efficacy o...

  • Borch, Troels HolzHerlev Hospital (författare)

Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor priming in patients with checkpoint inhibitor-resistant metastatic melanoma

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-07-01
  • BMJ,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:3b7a5845-040c-43da-8b93-d050ea3c29bc
  • https://lup.lub.lu.se/record/3b7a5845-040c-43da-8b93-d050ea3c29bcURI
  • https://doi.org/10.1136/jitc-2021-002703DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Harbst, KatjaLund 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(Swepub:lu)med-kbn (författare)
  • Rana, Aynal HaqueHerlev Hospital (författare)
  • Andersen, RikkeHerlev Hospital (författare)
  • Martinenaite, EvelinaHerlev Hospital (författare)
  • Kongsted, PerHerlev Hospital (författare)
  • Pedersen, MagnusHerlev Hospital (författare)
  • Nielsen, MortenHerlev Hospital (författare)
  • Kjeldsen, Julie WesterlinHerlev Hospital (författare)
  • Kverneland, Anders HandrupHerlev Hospital (författare)
  • Lauss, MartinLund 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(Swepub:lu)med-mlu (författare)
  • Hölmich, Lisbet RosenkrantzHerlev Hospital,University of Copenhagen (författare)
  • Hendel, HelleHerlev Hospital (författare)
  • Met, ÖzcanHerlev Hospital,University of Copenhagen (författare)
  • Jönsson, GöranLund 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(Swepub:lu)onk-gjo (författare)
  • Donia, MarcoUniversity of Copenhagen,Herlev Hospital (författare)
  • Marie Svane, IngeUniversity of Copenhagen,Herlev Hospital (författare)
  • Herlev HospitalLunds Melanomstudiegrupp (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal for ImmunoTherapy of Cancer: BMJ9:72051-1426

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