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PEGylated Recombinant Aplysia punctata Ink Toxin Depletes Arginine and Lysine and Inhibits the Growth of Tumor Xenografts.
- Source :
-
ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2024 Jun 10; Vol. 10 (6), pp. 3825-3832. Date of Electronic Publication: 2024 May 09. - Publication Year :
- 2024
-
Abstract
- In recent years, a novel treatment method for cancer has emerged, which is based on the starvation of tumors of amino acids like arginine. The deprivation of arginine in serum is based on enzymatic degradation and can be realized by arginine deaminases like the l-amino acid oxidase found in the ink toxin of the sea hare Aplysia punctata . Previously isolated from the ink, the l-amino acid oxidase was described to oxidate the essential amino acids l-lysine and l-arginine to their corresponding deaminated alpha-keto acids. Here, we present the recombinant production and functionalization of the amino acid oxidase Aplysia punctata ink toxin (APIT). PEGylated APIT (APIT-PEG) increased the blood circulation time. APIT-PEG treatment of patient-derived xenografted mice shows a significant dose-dependent reduction of tumor growth over time mediated by amino acid starvation of the tumor. Treatment of mice with APIT-PEG, which led to deprivation of arginine, was well tolerated.
- Subjects :
- Animals
Humans
Mice
Xenograft Model Antitumor Assays
Marine Toxins pharmacology
Marine Toxins therapeutic use
Marine Toxins chemistry
Recombinant Proteins pharmacology
Recombinant Proteins therapeutic use
L-Amino Acid Oxidase pharmacology
L-Amino Acid Oxidase metabolism
L-Amino Acid Oxidase chemistry
Female
Cell Line, Tumor
Arginine pharmacology
Arginine chemistry
Lysine pharmacology
Lysine chemistry
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacology
Aplysia
Subjects
Details
- Language :
- English
- ISSN :
- 2373-9878
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- ACS biomaterials science & engineering
- Publication Type :
- Academic Journal
- Accession number :
- 38722049
- Full Text :
- https://doi.org/10.1021/acsbiomaterials.4c00473