PEGylated Recombinant Ink Toxin Depletes Arginine and Lysine and Inhibits the Growth of Tumor Xenografts

Overview

Journal ACS Biomater Sci Eng

Publisher American Chemical Society

Specialties Biomedical Engineering
Biotechnology

Date 2024 May 9

PMID 38722049

Authors

Alena M Wolkersdorfer

Birgit Bergmann

Juliane Adelmann

Matthias Ebbinghaus

Eckhard Gunther

Marcus Gutmann

Lukas Hahn

Robert Hurwitz

Ralf Krahmer

Frank Leenders

Tessa Luhmann

Julia Schueler

Luisa Schmidt

Michael Teifel

Lorenz Meinel

Thomas Rudel

Affiliations

Soon will be listed here.

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 . 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.

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