CAR-T design: Elements and their synergistic function
Jayapriya Jayaraman,
Michael P. Mellody,
Andrew J. Hou,
Ruchi P. Desai,
Audrey W. Fung,
An Huynh Thuy Pham,
Yvonne Y. Chen,
Weian Zhao
Affiliations
Jayapriya Jayaraman
Department of Biomedical Engineering, University of California, Irvine, Irvine,CA,92697, United States
Michael P. Mellody
Department of Biomedical Engineering, University of California, Irvine, Irvine,CA,92697, United States
Andrew J. Hou
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095
Ruchi P. Desai
School of Medicine, University of California, Irvine, Irvine, CA, 92697
Audrey W. Fung
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697
An Huynh Thuy Pham
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697
Yvonne Y. Chen
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, 90095; Parker Institute for Cancer Immunotherapy Center, University of California, Los Angeles, Los Angeles, Los Angeles, 90095
Weian Zhao
Department of Biomedical Engineering, University of California, Irvine, Irvine,CA,92697, United States; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, United States; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, United States; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, United States; Edwards Life Sciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, CA 92697, United States; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, United States; Corresponding author.
Chimeric antigen receptor (CAR) T cells use re-engineered cell surface receptors to specifically bind to and lyse oncogenic cells. Two clinically approved CAR-T–cell therapies have significant clinical efficacy in treating CD19-positive B cell cancers. With widespread interest to deploy this immunotherapy to other cancers, there has been great research activity to design new CAR structures to increase the range of targeted cancers and anti-tumor efficacy. However, several obstacles must be addressed before CAR-T–cell therapies can be more widely deployed. These include limiting the frequency of lethal cytokine storms, enhancing T-cell persistence and signaling, and improving target antigen specificity. We provide a comprehensive review of recent research on CAR design and systematically evaluate design aspects of the four major modules of CAR structure: the ligand-binding, spacer, transmembrane, and cytoplasmic domains, elucidating design strategies and principles to guide future immunotherapeutic discovery.
