IN VITRO AND IN VIVO GENE DELIVERY TO IMMUNE EFFECTOR CELLS USING NANOPARTICLES FUNCTIONALIZED WITH DESIGNED ANKYRIN REPEAT PROTEINS (DARPINS)

摘要

The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8- targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8+ T cells in vitro and in vivo.