دورية أكاديمية
Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma
| العنوان: | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
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| المؤلفون: | De Santo, Carmela, Cheng, Paul, Beggs, Andrew, Egan, Sharon, Bessudo, Albert, Mussai, Francis |
| بيانات النشر: | Springer Verlag |
| سنة النشر: | 2018 |
| المجموعة: | University of Nottingham: Repository@Nottingham |
| مصطلحات موضوعية: | Arginase, Melanoma, Immunotherapy, Metabolism, BCT-100 |
| الوصف: | BackgroundMetastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism.Case presentationA 65-year-old patient with metastatic melanoma who progressed through two immunotherapy strategies with immune checkpoint inhibitor antibodies was enrolled in a phase I study (NCT02285101) and treated with 2 mg/kg intravenously, weekly pegylated recombinant arginase (BCT-100). The patient experienced no toxicities > grade 2 and entered a complete remission which is sustained for over 30 months. RNA-sequencing identified a number of transcriptomic pathway alterations compared to control samples. The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples.ConclusionsTargeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://nottingham-repository.worktribe.com/output/932822Test; Journal of Hematology and Oncology; Volume 11; https://nottingham-repository.worktribe.com/file/932822/1/melanoma%20s13045-018-0612-6.pdfTest |
| DOI: | 10.1186/s13045-018-0612-6 |
| الإتاحة: | https://doi.org/10.1186/s13045-018-0612-6Test https://nottingham-repository.worktribe.com/file/932822/1/melanoma%20s13045-018-0612-6.pdfTest https://nottingham-repository.worktribe.com/output/932822Test |
| حقوق: | openAccess |
| رقم الانضمام: | edsbas.77C7A7F1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13045-018-0612-6 |
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