Exploiting a type III interferon response to improve chemotherapeutic safety and efficacy

• DOI: 10.1016/j.ejps.2024.106974
• Publication Date: 2024-11-26T22:55:11Z
• Authors: Scott G. Tilden; Madison H. Ricco; Emily A. Hemann; Thomas J. Anchord...

Abstract Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase the efficacy of chemotherapeutic nanomedicines. In this study we sought to clarify which cell type(s) are capable of producing IFN-λ in response to lipoplexes and how the effects of IFN-λ are propagated. Additionally, we demonstrate that an IFN-λ pretreatment is also capable of altering the accumulation profile of small molecules like doxorubicin. Finally, we assessed different administration routes for an IFN-λ pretreatment and showed the ability of this pretreatment to significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.