Designed Ankyrin Repeat Protein (DARPin) to target chimeric antigen receptor (CAR)-redirected T cells towards CD4+ T cells to reduce the latent HIV+ cell reservoir

Abstract

Chimeric Antigen Receptor (CAR)-redirected T cells show great efficacy in the patient-specific therapy of hematologic malignancies. Here, we demonstrate that a DARPin with specificity for CD4 specifically redirects and triggers the activation of CAR engineered T cells resulting in the depletion of CD4+ target cells aiming for elimination of the human immunodeficiency virus (HIV) reservoir.

Chimeric antigen receptor engineered cells and their clinical application in infectious disease

“…constructed a design ankyrin repeat protein (DARPin)‐based CAR‐T targeting CD4 to reduce the viral reservoir of HIV. Compared with scFv, low‐grade expressed DARPins can still bind to a given target protein with high affinity without self‐aggregating, but the immunogenicity of DARPin in vivo should be taken into consideration for further evaluation 78 . At present, some DARPin‐CARs have entered the clinical trial stage, giving scientists great confidence (NCT02194426, NCT02462928 and NCT02462486) 79 …”