RECOMBINANT PROTEIN RIDA/UK114 IS EFFECTIVE IN REDUCING SOLID TUMOUR GROWTH IN VIVO

UK114 proteins, which serve as reactive intermediate deaminases, are well conserved across all life forms; while their exact functions remain not fully understood, they have shown potential as tumor antigens due to their expression in solid tumors. In this work, we have evaluated the activity of recombinant goat UK114 (UK114) protein, as a therapeutic agent in preclinical models of cancer. We have demonstrated that recombinant UK114 can diminish mouse mammary tumor growth when given as a vaccination, triggering the production of antibodies against tumor cells. Furthermore, the mutated UK114 protein did not induce production of specific antibodies and did not affect the tumor growth, indicating that the protein sequence is highly linked to UK114 immunomodulatory and enzymatic function, which drives the proteins anti-tumor effect. In a mouse model of cancer cachexia, the therapeutic use of UK114 effectively lessened tumor growth and alleviated cancer cachexia-associated weight loss. Notably, significant tumor reduction occurred when recombinant UK114 was therapeutically administered to immunodeficient mice with human cancer stem cell-induced lesions, indicating that the antitumoral effect of UK114 is not only due to immune activation, but also caused by other mechanisms, potentially related to proteins enzymatic detoxifying activity. Recombinant UK114 protein dual action as both immunomodulatory and detoxifying agent was demonstrated in various types of cancers in vivo and therefore, appears to be a promising new therapy reducing tumors in a complex systemic mechanism.