Carmela De Santo
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
Dr SHARON EGAN email@example.com
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.
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.
Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy.
De Santo, C., Cheng, P., Beggs, A., Egan, S., Bessudo, A., & Mussai, F. (2018). Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma. Journal of Hematology and Oncology, 11, Article 68. https://doi.org/10.1186/s13045-018-0612-6
|Journal Article Type||Article|
|Acceptance Date||May 2, 2018|
|Publication Date||May 18, 2018|
|Deposit Date||May 23, 2018|
|Publicly Available Date||May 23, 2018|
|Journal||Journal of Hematology and Oncology|
|Peer Reviewed||Peer Reviewed|
|Keywords||Arginase; Melanoma; Immunotherapy; Metabolism; BCT-100|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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