Journal
JOURNAL OF HEMATOLOGY & ONCOLOGY
Volume 11, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13045-018-0612-6
Keywords
Arginase; Melanoma; Immunotherapy; Metabolism; BCT-100
Categories
Funding
- Cancer Research UK
- MRC [MR/M009157/1] Funding Source: UKRI
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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.
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