Chimeric antigen receptor (CAR) T-cells have proven effective in hematologic malignancies targeting a restricted set of tumor-associated antigens. In this work, we demonstrate that CAR-T cells can be redirected to alternative tumor antigens through a switch protein adapter with antitumor efficacy in preclinical models.
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.