Inflammatory processes mediated by the immune system are a double-edged sword; they help contain threats, such as infections. However, an exacerbated inflammatory process can cause health problems. One way to regulate inflammation is using immunomodulators, such as human Dialyzable Leucocyte Extracts (hDLE). Transferon, an hDLE, decreases serum levels of TNF-α and IL-6, two pro-inflammatory cytokines, while increasing serum levels of IFN-γ, both in humans and in a murine model of Herpes Simplex Virus type I (HSV-1) infection [1, 2].

Monomeric Human Ubiquitin (mUb) was identified as the main peptide component in sequencing studies of oral Transferon [3]. Since then, a group of UDIBI researchers have been researching and developing mUb as an oral immunomodulator. They aim to determine its efficacy, toxicity, pharmacokinetics, mechanism of action (MoA) and target validation.

The development of mUb as a biotherapeutic implies solving two fundamental points: the study of a protein with oral therapeutic activity and the characterization of the MoA of a protein thought to be only relevant for intracellular functions.

Efficacy and toxicity studies are currently carried out at the UDIBI using in vivo, in vitro and in silico models. To date, mUb, administered orally, has been shown to increase the survival of HSV1-infected mice [4]. In silico methods have demonstrated that mUb binds to the CXCR-4 receptor, the proposed extracellular receptor for this molecule.

The development of mUb is being carried out with self-generated resources and driven by UDIBI’s interest in offering an innovative biological product to society. We hope to launch a ubiquitin-derived helpful product to treat exacerbated inflammatory processes in the subsequent years.

1. Estrada-Parra S, et al. Comparative study of transfer factor and acyclovir in the treatment of herpes zoster. Int J Immunopharmacol. 1998 Oct;20(10):521-35. doi: 10.1016/s0192-0561(98)00031-9. PMID: 9839657.
2. Salinas-Jazmín N, et al. Herpes murine model as a biological assay to test dialyzable leukocyte extracts activity. J Immunol Res. 2015;2015:146305. doi: 10.1155/2015/146305. Epub 2015 Apr 23. PMID: 25984538; PMCID: PMC4423021.
3. Vallejo-Castillo L, et al. Sequencing Analysis and Identification of the Primary Peptide Component of the Dialyzable Leukocyte Extract “Transferon Oral”: The Starting Point to Understand Its Mechanism of Action. Front Pharmacol. 2020 Oct 7;11:569039. doi: 10.3389/fphar.2020.569039. PMID: 33117165; PMCID: PMC7577238.
4. Saini V, et al. Structural determinants of ubiquitin-CXC chemokine receptor 4 interaction. J Biol Chem. 2011 Dec 23;286(51):44145-44152. doi: 10.1074/jbc.M111.298505. Epub 2011 Oct 28. PMID: 22039044; PMCID: PMC3243501.