Use Of Methionine Gamma-Lyase-Loaded Erythrocytes To Induce Effective Methionine Depletion In Cancer Therapy

Methionine (Met) dependence is a cancer-specific metabolic defect that has emerged as a target during the last two decades. The use of methionine gamma-lyase (MGL; EC number 4.4.1.11), a bacterial Met-catabolizing enzyme, is a promising strategy for treatment of Met-dependent cancers. However, one challenge is that MGL has a very short half-life (~2 hours), resulting in a short-term Met depletion in vivo. Additionally, its cofactor, pyridoxal 5’-phosphate (PLP) is rapidly eliminated from plasma (Yang et al., 2004). PEGylation extends the MGL half-life in mice to up to 38 hours. Nevertheless, frequent injections are still necessary for maintaining an effective Met depletion over time (Sun et al., 2003). In addition, the low bioavailability of PLP remains a major hurdle due to both scavenging by plasma proteins and very short half-life ( Citation Format: Fabien Gay, Karine Aguera, Karine Senechal, Philip Lorenzi, Alexander Scheer, Francoise Horand, Vanessa Bourgeaux. Use of methionine gamma-lyase-loaded erythrocytes to induce effective methionine depletion in cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2134. doi:10.1158/1538-7445.AM2017-2134