Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma
Background Metastatic 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,...
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| Format: | Article |
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BioMed Central
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51989/ |
| _version_ | 1848798620889907200 |
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| author | De Santo, Carmela Cheng, Paul Beggs, Andrew Egan, Sharon Bessudo, Albert Mussai, Francis |
| author_facet | De Santo, Carmela Cheng, Paul Beggs, Andrew Egan, Sharon Bessudo, Albert Mussai, Francis |
| author_sort | De Santo, Carmela |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background
Metastatic 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 presentation
A 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.
Conclusions
Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy. |
| first_indexed | 2025-11-14T20:22:40Z |
| format | Article |
| id | nottingham-51989 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:22:40Z |
| publishDate | 2018 |
| publisher | BioMed Central |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-519892020-05-04T19:36:43Z https://eprints.nottingham.ac.uk/51989/ Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma De Santo, Carmela Cheng, Paul Beggs, Andrew Egan, Sharon Bessudo, Albert Mussai, Francis Background Metastatic 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 presentation A 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. Conclusions Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy. BioMed Central 2018-05-18 Article PeerReviewed De Santo, Carmela, Cheng, Paul, Beggs, Andrew, Egan, Sharon, Bessudo, Albert and Mussai, Francis (2018) Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma. Journal of Hematology and Oncology, 11 . 68/1-68/5. ISSN 1756-8722 Arginase; Melanoma; Immunotherapy; Metabolism; BCT-100 https://jhoonline.biomedcentral.com/articles/10.1186/s13045-018-0612-6 doi:10.1186/s13045-018-0612-6 doi:10.1186/s13045-018-0612-6 |
| spellingShingle | Arginase; Melanoma; Immunotherapy; Metabolism; BCT-100 De Santo, Carmela Cheng, Paul Beggs, Andrew Egan, Sharon Bessudo, Albert Mussai, Francis Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title_full | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title_fullStr | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title_full_unstemmed | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title_short | Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| title_sort | metabolic therapy with peg-arginase induces a sustained complete remission in immunotherapy-resistant melanoma |
| topic | Arginase; Melanoma; Immunotherapy; Metabolism; BCT-100 |
| url | https://eprints.nottingham.ac.uk/51989/ https://eprints.nottingham.ac.uk/51989/ https://eprints.nottingham.ac.uk/51989/ |