Exploiting a Type III Interferon Response to Improve Chemotherapeutic Safety and Efficacy

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.