A Switch Protein Adapter for Anti‐LILRB4 CAR‐T Cells

Abstract

Chimeric antigen receptor‐T cell (CAR‐T) immunotherapy has shown remarkable results for the treatment of certain hematologic malignancies. A redirection strategy that utilizes clinically relevant CAR‐T cells in combination with adapter proteins may be an effective strategy to target other hematologic and solid cancers. We established a fusion antibody‐based strategy with flexibility to target multiple tumor types in combination with a novel anti‐leukocyte immunoglobulin‐like receptor‐B 4 (LILRB4) CAR‐T cell. Specifically, we engineered switch protein (SwP) adapters containing the LILRB4 extracellular domain fused to either an anti‐CD19 or anti‐CD20 single‐chain variable fragment (scFv). These SwPs were sufficient to stimulate anti‐LILRB4 CAR‐T cells against SwP‐tagged LILRB4‐CD19+ and LILRB4‐CD20+ cancers in vitro and in vivo. This strategy may allow CAR‐T cells to be redirected against a variety of tumor antigens and cancer types and become a valuable approach to expand the impact of cellular immunotherapy.