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DRUG:

pegylated recombinant human arginase (BCT-100)

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Other names: BCT-100, PEG-BCT-100, rhArgIpeg5000, rhArg1, BCT 100, BCT100
Company:
BCT international
Drug class:
Arginase replacement
1m
PEG-BCT-100 and canavanine synergistically induce apoptosis in arginine biosynthetic enzyme-deficient pancreatic cancer. (PubMed, Cancer Res Commun)
From our in-house cohort and online database analysis, we found that the majority of the pancreatic cancer patients exhibited deficiencies in both ASS1 and OTC enzymes, suggesting that the combination of arginine deprivation and canavanine could be particularly effective in these patients. The ASS1- and OTC-negativity could also serve as predictive biomarkers for the response in other arginine-dependent cancers.
Journal
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ASS1 (Argininosuccinate synthase 1)
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pegylated recombinant human arginase (BCT-100)
1year
Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells. (PubMed, EMBO Rep)
Moreover, BCT-100 is highly efficacious in a patient-derived xenograft model, causing > 90% reduction in the number of human leukaemic stem cells (LSCs). These findings indicate arginine depletion to be a promising and novel strategy to eradicate therapy resistant LSCs.
Journal
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CD34 (CD34 molecule) • ASS1 (Argininosuccinate synthase 1)
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pegylated recombinant human arginase (BCT-100)
over2years
Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy. (PubMed, Lung Cancer (Auckl))
Small cell lung cancer (SCLC) displays marked arginine auxotrophy due to inactivation of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1), and as a consequence may be targeted with pegylated arginine deiminase or ADI-PEG20 (pegargiminase) and human recombinant pegylated arginases (rhArgPEG, BCT-100 and pegzilarginase). Moreover, recent work has identified an intriguing role for targeting arginine in combination with PD-1/PD-L1 immune checkpoint inhibitors and clinical trials are in progress. Thus, future studies of arginine-depleting agents with chemoimmunotherapy, the current standard of care for SCLC, may lead to enhanced disease control and much needed improvements in long-term survival for patients.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-1 (Programmed cell death 1) • ASS1 (Argininosuccinate synthase 1)
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Hepacid (pegargiminase) • pegylated recombinant human arginase (BCT-100) • Loargys (pegzilarginase)
over2years
Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion. (PubMed, Biomed Res Int)
Pegylated arginase (BCT-100) is currently in phase I/II trials in relapsed pHGG. Our results suggest that therapeutic arginine depletion may also be useful in other tumour types and IHC analysis of patient tumour samples could help identify patients likely to benefit from this treatment.
Journal
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ASS1 (Argininosuccinate synthase 1) • ARG2 (Arginase 2)
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pegylated recombinant human arginase (BCT-100)
almost3years
Pegylated arginase isolated from beef liver tissue inhibited cell proliferation, induced apoptosis & inhibits induced mammary tumors in human breast cancer in vitro & in vivo (AACR 2022)
Furthermore, the results also revealed a significant reduction in activities of ALT, AST, and ALP in the Peg-Arginase group compared to MNU untreated or native-Arginase groups, suggesting that Peg-Arginase may eliminate the hepatotoxic effect of the MNU. All in all, our results suggested that the arginine-depleting enzyme, Peg-Arginase, exerted an anticancer effect against both T-47D and MDA-MB-231 breast cancer cell lines through cell proliferation inhibition and apoptosis induction.
Preclinical
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TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CASP3 (Caspase 3) • MIR23A (MicroRNA 23a)
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TP53 mutation • CCND1 mutation
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pegylated recombinant human arginase (BCT-100)
over3years
A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma. (PubMed, Invest New Drugs)
PEG-BCT-100 in chemo naïve post-sorafenib HCC is well tolerated with moderate DCR. ASS-negative confers OS advantage over ASS-positive HCC. ASS-negativity is a potential biomarker for OS in HCC and possibly for other ASS-negative arginine auxotrophic cancers.
Clinical • P2 data • Journal
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ASS1 (Argininosuccinate synthase 1)
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sorafenib • pegylated recombinant human arginase (BCT-100)
4years
Preclinical safety and antitumor activity of the arginine-degrading therapeutic enzyme pegzilarginase, a PEGylated, cobalt-substituted recombinant human arginase 1. (PubMed, Transl Res)
This is consistent with the known autophagy-inducing effects of arginine depletion, and the link between autophagy and major histocompatibility complex antigen presentation to T cells. Our work supports the ongoing clinical investigations of pegzilarginase in solid tumors and clinical combination of pegzilarginase with immune checkpoint inhibitors.
Journal
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CD8 (cluster of differentiation 8) • ASS1 (Argininosuccinate synthase 1)
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TILs
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pegylated recombinant human arginase (BCT-100) • Loargys (pegzilarginase)