Synthetic Biology Journal ›› 2023, Vol. 4 ›› Issue (2): 373-393.doi: 10.12211/2096-8280.2022-063

• Invited Review • Previous Articles     Next Articles

Synthetic biology and engineered T cell therapy

Junhong XIE1, Jingjing HE2, Penghui ZHOU3   

  1. 1.National Center for International Research of Bio-targeting Theranostics,Guangxi Key Laboratory of Bio-targeting Theranostics,Guangxi Medical University,Nanning 530021,Guangxi,China
    2.Medical Research Department,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510055,Guangdong,China
    3.State Key Laboratory of Oncology in Southern China,Sun Yat-sen University Cancer Center,Guangzhou 510060,Guangdong,China
  • Received:2022-11-17 Revised:2023-02-01 Online:2023-04-30 Published:2023-04-27
  • Contact: Jingjing HE, Penghui ZHOU


In recent years, engineering T cell therapy has made great progress in tumor immunotherapy, which mainly includes T-cell receptor-engineered T cell (TCR-T) therapy and chimeric antigen receptor T cell (CAR-T) therapy. Due to their structure difference, TCR-T and CAR-T cells show different characteristics in signal activation and antigen recognition. CAR has scFv derived from antibody, containing CD3ζ and costimulatory domain(s), making engineered CAR able to recognize specific tumor associated antigens. Therefore, CAR has an ability to bind unprocessed tumor surface antigens without MHC processing, while TCR engages with both tumor intracellular and surface antigens embedded in MHC. While CAR-T cell therapy has demonstrated a significant clinical effect against malignant blood tumors, TCR-T cell therapies have been tested in hematological and solid tumors. Even though clinical results are encouraging for both approaches, several major challenges have been identified, including: target antigen selection such as less tumor toxicity and antigen escape, T cell homing to the tumor, T cell infiltration into the tumor, T cell persistence, and local immunosuppression in the tumor microenvironment. Synthetic biology technologies have enabled flexible reprogramming of engineered T cells to overcome the aforementioned limitations, bringing new opportunities for improving their safety and effectiveness, but the choice of a suitable target antigen is still a key for success. Moreover, improved preclinical TCR/CAR screening is likely to enhance the safety of engineered T cell therapies, and additional T cell engineering to further enhance engineered T cells at various levels has generated promising results, including: (1) modulation of affinity, (2) safety control elements, and (3) targeting TME components. Future developments will likely harness combinatorial strategies to overcome challenges posed by the tumors. In this article, we address structure and signal activation, target selection, affinity optimization, safety modification and gene editing strategies for engineered T cells, and also review the potential synthetic biological approaches and latest progress of engineered T cell therapy in the application of tumor immunotherapy.

Key words: synthetic biology, engineering T cell therapy, TCR-T, CAR-T, tumor immunotherapy

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