Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma

Journal of Hematology & Oncology
Carmela De SantoFrancis Mussai

Abstract

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 val...Continue Reading

References

Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dusan BogunovicNina Bhardwaj
Aug 7, 2012·Investigational New Drugs·Patrick A OttJedd D Wolchok
Feb 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michele MaioJedd D Wolchok
Jan 27, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Georgina V LongKeith T Flaherty
Feb 26, 2016·International Journal of Cancer. Journal International Du Cancer·Livingstone FultangFrancis Mussai
Sep 12, 2017·The New England Journal of Medicine·Jeffrey WeberUNKNOWN CheckMate 238 Collaborators
Nov 24, 2017·International Journal of Cancer. Journal International Du Cancer·Carmela De SantoFrancis Mussai

❮ Previous
Next ❯

Citations

Jan 31, 2019·Journal of Leukocyte Biology·Ricardo A León-LetelierEzequiel M Fuentes-Pananá
Jun 5, 2019·Genes & Development·Laura Poillet-Perez, Eileen White
Apr 8, 2020·Frontiers in Pharmacology·Abdelrahman Y FoudaRuth B Caldwell
Jul 30, 2020·International Journal of Molecular Sciences·Gonçalo S ClementePhilip H Elsinga
Dec 14, 2018·Cancer Research·Livingstone FultangFrancis Mussai
Jan 5, 2021·Chinese Medical Journal·Jin-Shou YangLei You
Feb 5, 2021·Cancers·Barbara Seliger, Chiara Massa
Mar 28, 2021·European Journal of Medicinal Chemistry·Jingyu ZhangXiaowu Dong
May 1, 2021·Cancers·Josep Tarragó-Celada, Marta Cascante
Jul 25, 2021·Cancers·Chia-Lin ChenHsing-Jien Kung
Jul 27, 2021·Cancer Chemotherapy and Pharmacology·Neha Kumari, Saurabh Bansal
Jun 17, 2020·ACS Applied Materials & Interfaces·Jing GuQunyou Tan

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
xenografts

Clinical Trials Mentioned

NCT02285101

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cellular Immunometabolism

Immunometabolism involves not only the way metabolites are digested by the immune system, but the way in which they can alter the pathway of the immune system. These responses occur in day-to-day healthy cell functioning, but can result in diseases, such as autoimmune disorders. Discover the latest research on cellular immunometabolism here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.