Abstract
High-grade neuroblastomas (NB) have a poor prognosis, and there is a need to explore novel therapies. Natural killer (NK) cells rapidly lyse target cells without prior exposure, and serve as a promising source for adoptive cell therapy, however availability from adult donors is limited. Cord blood (CB) derived NK cells have promise as an ideal source for “off the shelf” therapy as they can be selected for optimally mismatched donors. However, CB NK cell efficacy is limited by the immunosuppressive microenvironment in solid tumors such as NB, where high levels of secreted TGFβ actively impairs NK cell activity. To overcome this, we genetically-modified NK cells to express a modified TGFβ receptor which contains an activation domain, and is thus able to engage with TGFβ while potentially converting downstream signals to enhance NK cell function.
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