info:eu-repo/semantics/article
Development of highly stable and de-immunized versions of recombinant alpha interferon: promising candidates for the treatment of chronic and emerging viral diseases
Fecha
2021-12Registro en:
Giorgetti, Sofia Inés; Etcheverrigaray, Marina; Terry, Frances; Martin, William; De Groot, Anne Searls ; et al.; Development of highly stable and de-immunized versions of recombinant alpha interferon: promising candidates for the treatment of chronic and emerging viral diseases; Elsevier; Clinical Immunology; 233; 12-2021; 1-12
1521-6616
CONICET Digital
CONICET
Autor
Giorgetti, Sofia Inés
Etcheverrigaray, Marina
Terry, Frances
Martin, William
De Groot, Anne Searls
Ceaglio, Natalia Analia
Oggero Eberhardt, Marcos Rafael
Mufarrege, Eduardo Federico
Resumen
Human interferon alpha (hIFN-α) administration constitutes the current FDA approved therapy for chronic Hepatitis B and C virus infections. Additionally, hIFN-α treatment efficacy was recently demonstrated in patients with COVID-19. Thus, hIFN-α constitutes a therapeutic alternative for those countries where vaccination is inaccessible and for people who did not respond effectively to vaccination. However, hIFN-α2b exhibits a short plasma half-life resulting in the occurrence of severe side effects. To optimize the cytokine's pharmacokinetic profile, we developed a hyperglycosylated IFN, referred to as GMOP-IFN. Given the significant number of reports showing neutralizing antibodies (NAb) formation after hIFN-α administration, here we applied the DeFT (De-immunization of Functional Therapeutics) approach to develop functional, de-immunized versions of GMOP-IFN. Two GMOP-IFN variants exhibited significantly reduced ex vivo immunogenicity and null antiproliferative activity, while preserving antiviral function. The results obtained in this work indicate that the new de-immunized GMOP-IFN variants constitute promising candidates for antiviral therapy.