Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β
Kajal Chaudhry, Ashley Geiger, Ehsan Dowlati, Haili Lang, Danielle Sohai, Eugene Hwang, Christopher A. Lazarski, Eric Yvon, Matthias Holdhoff, R. Brad Jones, Barbara Savoldo, Carolina Colli Cruz, Catherine M. Bollard
Abstract
. However, transforming growth factor (TGF)-β within the tumor microenvironment has devastating effects on the cytolytic activity of both unmodified and CAR-transduced NK cells. To overcome this potent immune suppression, we demonstrated that co-transducing NK cells with a B7H3 CAR and a TGF-β dominant negative receptor (DNR) preserves cytolytic function in the presence of exogenous TGF-β. This study demonstrates that a novel DNR and CAR co-expression strategy may be a promising therapeutic for recalcitrant CNS tumors like GBM.
Topics & Concepts
Chimeric antigen receptorCancer researchCytolysisImmune systemImmunologyTransforming growth factorInterleukin 12In vivoBiologyImmunotherapyCytotoxic T cellIn vitroCell biologyBiotechnologyBiochemistryCAR-T cell therapy researchImmune Cell Function and InteractionT-cell and B-cell Immunology