Academic Journal

Synthetic Immunotherapy: Programming Immune Cells with Novel and Sophisticated Logic Capabilities.

Bibliographic Details
Title: Synthetic Immunotherapy: Programming Immune Cells with Novel and Sophisticated Logic Capabilities.
Authors: Lam CK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska. Electronic address: calvin.lam@unmc.edu., Hyde RK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska., Patel SA; Division of Hematology Oncology, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska.
Source: Transplantation and cellular therapy [Transplant Cell Ther] 2022 Sep; Vol. 28 (9), pp. 560-571. Date of Electronic Publication: 2022 Jun 10.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101774629 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-6367 (Electronic) Linking ISSN: 26666367 NLM ISO Abbreviation: Transplant Cell Ther Subsets: MEDLINE
Imprint Name(s): Original Publication: [New York] : Elsevier Inc., [2021]-
MeSH Terms: Immunotherapy* , Receptors, Antigen, T-Cell*, Immunologic Factors ; Immunotherapy, Adoptive ; Logic ; T-Lymphocytes
Abstract: The development of chimeric antigen receptor (CAR) T cells began as a means toward specific yet modular therapies against cancer. Recent advancements in several CAR T cell therapies show the promise of cellular immunotherapy in cancer treatment. CAR T cell therapy is still immature, however, and improvements are needed to fully realize its curative potential. The approved CAR T cells are designed with simple logic capabilities; an antigen sensor that, when bound to the target antigen, triggers costimulation domains and native T cell activation. This single-type sensor and native activation design, although capable, also has severe limitations. Reliance on a single-type sensor leads to unwanted toxicity toward antigen-expressing normal tissues, and unmodulated activation leads to unwanted cytokine toxicity. Synthetic biology (SB) offers a powerful solution to these limitations: modular receptors with customizable sensors and output behaviors that enable higher Boolean logic. SB T cells already have shown incredible capabilities, such as multiple-antigen discrimination and improved persistence. In light of these results, cellular immunotherapy may already be branching into a new subfield that we term here as "synthetic immunotherapy." Here we review the current logic capabilities of CAR T cells, the resulting limitations, and the engineering undertaken to address these issues. We then discuss several tools of SB and show how SB CAR T cells pave the way for synthetic immunotherapy.
(Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Contributed Indexing: Keywords: CAR T cell; Cell engineering; Cellular immunotherapy; Synthetic biology; Synthetic biology CAR T cell; Synthetic immunotherapy; Synthetic receptors
Substance Nomenclature: 0 (Immunologic Factors)
0 (Receptors, Antigen, T-Cell)
Entry Date(s): Date Created: 20220612 Date Completed: 20220830 Latest Revision: 20220923
Update Code: 20221216
DOI: 10.1016/j.jtct.2022.06.001
PMID: 35691572
Database: MEDLINE
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