Ssemadaali, M. A., Newmyer, S., Radhakrishnan, H., Arredondo, J., Javitz, H. S., Dandekar, S., & Bhatnagar, P. (2022). Antiviral T-cell Biofactory platform for SARS-CoV-2. bioRxiv, 2022-06.
Vaccines help reduce new infections, but interventions that can prevent the disease from transitioning to a severe stage are rather limited. Dysregulated IFN kinetics are mostly exploited by pathogenic viruses, including SARS-CoV-2. The clinical benefits of systemically infused IFN are, unfortunately, mired by undesired side effects. To address this situation, we engineered a T cell to synthesize interferons (IFNs) as antiviral proteins upon recognizing the virus envelop protein of SARS-CoV-2, i.e., anti-SARS T-cell Biofactory. The T-cell Biofactory, capable of regulating the IFN expression with spatiotemporal resolution within the infected tissues, can mitigate these concerns. In this work, we determined the prophylactic and therapeutic effects of the type-I and type-III IFNs produced from the T-cell Biofactory against SARS-CoV-2 infection in host cells and investigated the expression profiles of ensuing IFN-stimulated genes (ISGs). To enable the translation of T-cell Biofactory as an effective antiviral countermeasure, we also investigated an irradiation dose that renders the T-cell Biofactory non-proliferative and thus non-oncogenic. The ongoing public health crisis motivated us to direct the T-cell Biofactory technology to target SARS-CoV-2. The T-cell Biofactory, based on T cells engineered with chimeric antigen receptors (CAR T cells), is a platform technology that can be rapidly re-engineered and become available for targeting any new pathogen.