Language
English
Publication Date
2-1-2025
Journal
European Journal of Immunology
DOI
10.1002/eji.202451172
PMID
39663681
PMCID
PMC12208297
PubMedCentral® Posted Date
6-30-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Humans, Receptors, Immunologic, Immunotherapy, Adoptive, Receptors, Chimeric Antigen, Animals, Antigens, CD19, Mice, T-Lymphocytes, Single-Chain Antibodies, Cell Line, Tumor, Neoplasms, Antigens, CD20, Membrane Glycoproteins, cancer, chimeric antigen receptor-T (CAR-T), inhibitory receptor, leukocyte immunoglobulin-like receptor-B 4 (LILRB4), switch protein, tumor microenvironment, universal chimeric antigen receptor-T (CAR-T)
Published Open-Access
yes
Recommended Citation
Huang, Ryan; Chen, Heyu; Xie, Jingjing; et al., "A Switch Protein Adapter for Anti-LILRB4 CAR-T Cells" (2025). The Brown Foundation: Institute of Molecular Medicine. 7.
https://digitalcommons.library.tmc.edu/molecular_med/7