Abstract

Universal Chimeric Antigen Receptor T cells (CAR T), an alternative design based on conventional CAR T cells, uses a switchable adaptor for a better redirection towards the target site. This technology overcomes the obstacles of the conventional Car T cells system, such as immunogenicity, massive expression of cytokine and fixed antigen specificity. This article introduces universal CAR T cells from both the perspectives of the universal T cells and its modular CAR systems, illustrating the advancement of universal CAR T cells to overcome the limitation of conventional CAR T cells and serve as a more controllable and highly promising system. The universal CAR T cells section focuses on the challenges of choosing T cell sources and the corresponding solutions, while the modular CAR system section summarizes the different types of switchable adaptors in combination with clinical applications in various types of cancer treatments. Overall, universal CAR T cells therapy is a novel development that not only out-competes but also recovers the shortage of the conventional CAR T cells system. With the use of switchable adaptors, the universal CAR T cells system is commercially beneficial for the public and a safe product to allow the industry to expand the clinical application of different types of cancers.

Highlights

  • Chimeric Antigen Receptor (CAR) T cell therapy has been demonstrated as a potent anti-cancer therapeutic

  • Immunogenicity is another issue caused by host cells rejecting transferred allogeneic CAR T cells due to “foreign” proteins presented on CARs and T cells

  • The universal modular CAR system has shown its high efficiency in clinical application, reducing cytokine release syndrome, antigen loss, and the risk of GVHD

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Summary

Introduction

Chimeric Antigen Receptor (CAR) T cell therapy has been demonstrated as a potent anti-cancer therapeutic. The development of universal T cells focuses on developing ready-to-use off-the-shelf universal allogeneic T cell or CAR T cell products This will overcome the limitations of manufacturing conventional CAR T cell therapies and make them more accessible and beneficial to a larger population. The development of modular CAR systems aims to design a CAR system that could be redirected to targeting different tumor-associated antigens (TAA) This will offer better flexibility, controllability, and safety compared to conventional CAR T cell therapies. Universal CAR T cells can efficiently target different types of cancers such as infant B-cell acute lymphoblastic leukemia, hepatocellular carcinoma, acute myeloid leukemia with the use of different modulators Such a system can precisely target the cancer cell receptors, lowering the risk of graft vs host disease, cytokine release syndrome (CRS), and the potential of antigen loss. The universal CAR T cell system is more pervasive to patients and is used to target cancers that conventional CAR T cell therapy cannot treat cancers

Engineering of universal T cells
Challenges and Strategies of Engineering of universal T cells
Immunogenicity
Strategies to overcome GVHD and immunogenicity
T cell-subset selection
Gene editing approaches
Universal Modular CAR system
Modular CAR systems’ Structure
Choices of Switch elements and different characteristics
Overcome antigen loss relapse and heterogeneous tumor population
Expand the use of targeting elements
Enhanced treatment safety
Universal CAR T cell real case studies
Findings
Conclusion
Full Text
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