Institute of Pharmacy and Food Chemistry, University of Würzburg, 97074 Würzburg, Germany.
Chair of Microbiology, Biocentre, University of Würzburg, 97074 Würzburg, Germany.
ACS Biomater Sci Eng. 2024 Jun 10;10(6):3825-3832. doi: 10.1021/acsbiomaterials.4c00473. Epub 2024 May 9.
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 . 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 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.
近年来，一种新的癌症治疗方法已经出现，这种方法基于肿瘤对精氨酸等氨基酸的饥饿。血清中精氨酸的剥夺是基于酶的降解，可以通过存在于海兔墨汁中的 l-氨基酸氧化酶等精氨酸脱氨酶来实现。l-氨基酸氧化酶以前从墨汁中分离出来，据描述可以将必需氨基酸 l-赖氨酸和 l-精氨酸氧化为相应的脱氨基α-酮酸。在这里，我们介绍了氨基酸氧化酶 墨汁毒素（APIT）的重组生产和功能化。聚乙二醇化 APIT（APIT-PEG）增加了血液循环时间。APIT-PEG 处理患者来源的异种移植小鼠显示，随着时间的推移，肿瘤的氨基酸饥饿介导的肿瘤生长显著呈剂量依赖性减少。APIT-PEG 处理导致精氨酸缺乏的小鼠耐受性良好。
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