CD4 T-cell platform for delivering interferons as an antiviral countermeasure with a focus on SARS-CoV-2.

Vaccines prevent the incidence of new infections, but availability of interventions that can prevent transition to severe disease is limited. Interferons (IFN) serve an important part of anti-viral host immune defense. Viruses including SARS-CoV-2 dysregulate IFN kinetics, leading to pathogenesis. The efficacy of systemically infused IFNs as a viable antiviral intervention is compromised by their adverse side effects and restrict the acceptable dosage levels. To address this problem, CD4 T cells have been engineered into a cell-based delivery platform that synthesizes antiviral IFNs upon recognizing the envelope protein of SARS-CoV-2. This pathway cannot be disrupted by viruses and delivers the IFNs directly where needed, reducing side effects. Prophylactic and therapeutic effects of the type-I and type-III IFNs, produced from the T-cell delivery platform, on SARS-CoV-2-infected host cells have been determined. Among the tested interferons, type-I IFN-β consistently exhibited the strongest antiviral activity. The platform is based on CD4 T cells engineered with chimeric antigen receptors and can be rapidly re-engineered for targeting any new pathogen with sensitivity toward IFNs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-025-01420-1.