Can Engineering IL-2Rα Expression Improve NK Cell Immunotherapy?

Abstract Natural killer (NK) cells are innate lymphocytes central to anti-viral and anti-tumour responses. Activated NK upregulate IL-2Rα, promoting the formation of a high-affinity heterotrimeric IL-2Rαβγ that mediates cell expansion enhances cytotoxicity. Several applications cancer immunotherapy, including using chimeric antigen receptors (CAR), have shown early success in clinical studies. Allogeneic can illicit activity without toxicities, making them attractive for biomanufactured “off-the-shelf” immunotherapy. Following adoptive transfer, low-dose IL-2 injections commonly administered enhance activity. However, expansion, persistence, tumour clearance remain largely inadequate. Moreover, regulatory T (Tregs) use their IL-2Rα expression sequester injected IL-2, leading Treg suppression. We hypothesize CAR therapy be improved by engineering high alongside CAR. predict resulting CAR-IL2Rα will more sensitive injections. used lentiviral transduction multicistronic transgene force I found were responsive in-vitro than conventional cells. This novel strategy may improve enhancing persistence activity, limiting suppression microenvironment. NRC Disruptive Technology Solutions Cell Gene Therapy Challenge Program Canadian Institutes Health Research