Universal CARs, universal T cells, and universal CAR T cells

Juanjuan Zhao,Yongping Song,Quande Lin,Delong Liu

doi:10.1186/s13045-018-0677-2

Juanjuan Zhao, Yongping Song + Show 2 more

Open Access

https://doi.org/10.1186/s13045-018-0677-2

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Abstract

Currently, the two approved T cell products with chimeric antigen receptors (CAR) are from autologous T cells. These CAR T cells approved for clinical use must be generated on a custom-made basis. This case-by-case autologous T cell production platform remains a significant limiting factor for large-scale clinical application due to the costly and lengthy production process. There is also an inherent risk of production failure. The individualized, custom-made autologous CAR T cell production process also posts constriction on the wide application on diverse tumor types. Therefore, universal allogeneic T cells are needed for the preparation of universal CAR T cells that can serve as the “off-the-shelf” ready-to-use therapeutic agents for large-scale clinical applications. Genome-editing technologies including ZFN (zinc finger nuclease), TALEN (transcription activator-like effector nuclease), and CRISPR-Cas9 are being used to generate the universal third-party T cells. In addition, split, universal, and programmable (SUPRA) CARs are being developed to enhance the flexibility and controllability of CAR T cells. The engineered universal T cells and universal CARs are paving the road for a totally new generation of CAR T cells capable of targeting multiple antigens and/ or being delivered to multiple recipients without re-editing of T cells. This may escalate to a new wave of revolution in cancer immunotherapy. This review summarized the latest advances on designs and development of universal CARs, universal T cells, and clinical application of universal CAR T cells.

Highlights

Chimeric antigen receptors (CARs) are engineered receptors that typically contain the antigen-binding region of a monoclonal antibody, T cell receptor transmembrane domain, and an intracellular signaling domain of CD3 zeta chain [1–7]
This review summarized the recent advances in the designs and applications of universal CAR T cells
Universal CARs: design principles and early studies The current CAR T cell therapy is limited by antigen specificity and scalability since each CAR T cell system targets only one antigen or two antigens [24]

Summary

Introduction

Chimeric antigen receptors (CARs) are engineered receptors that typically contain the antigen-binding region of a monoclonal antibody (mAb), T cell receptor transmembrane domain, and an intracellular signaling domain of CD3 zeta chain [1–7]. Universal CARs: design principles and early studies The current CAR T cell therapy is limited by antigen specificity and scalability since each CAR T cell system targets only one antigen or two antigens [24]. This BBIR platform of universal CAR system has the potential to significantly extend conventional CAR approaches and generate T cells of unlimited antigen specificity.

Results

Conclusion