Journal
SEMINARS IN CANCER BIOLOGY
Volume 94, Issue -, Pages 34-49Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2023.05.009
Keywords
CAR therapy; Computational modeling; Systems biology; Immunology; Intracellular signaling
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CAR therapy is a revolutionary approach to cancer treatment that involves engineering immune cells with an artificial receptor to recognize and eliminate tumor cells. Systems and computational biology techniques have been used to understand the mechanisms and improve the design of CAR therapy.
In the recent decades, chimeric antigen receptor (CAR) therapy signaled a new revolutionary approach to cancer treatment. This method seeks to engineer immune cells expressing an artificially designed receptor, which would endue those cells with the ability to recognize and eliminate tumor cells. While some CAR therapies received FDA approval and others are subject to clinical trials, many aspects of their workings remain elusive. Techniques of systems and computational biology have been frequently employed to explain the operating principles of CAR therapy and suggest further design improvements. In this review, we sought to provide a comprehensive account of those efforts. Specifically, we discuss various computational models of CAR therapy ranging in scale from organismal to molecular. Then, we describe the molecular and functional properties of costimulatory domains frequently incorporated in CAR structure. Finally, we describe the signaling cascades by which those cos-timulatory domains elicit cellular response against the target. We hope that this comprehensive summary of computational and experimental studies will further motivate the use of systems approaches in advancing CAR therapy.
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