Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into the<i>CD247</i>locus

Lah, Sangjoon; Kim, Segi; Kang, In Man; Kim, Hyojin; Hupperetz, Cedric; Jung, Hyuncheol; Choi, Hyeong Ryeol; Lee, Young-Ho; Jang, Hyeon-Ki; Bae, Sangsu; Kim, Chan Hyuk

doi:10.1136/jitc-2022-005519

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…Recent studies have reported that the insertion of 4-1BB into the TCR structure can enhance the activation signals within T cells, but the location of 4-1BB relative to the CD3ζ domain (N-terminal or C-terminal) significantly affects TCR formation. The fusion of the 4-1BB domain to the N-terminal of CD3ζ could fail to constitute the TCR complex 16 . As for CAR, the location preference for co-stimulatory signaling domain modification is reversed, reflecting another significant structural difference.…”

Section: Synthetic Receptors For Programing T Cellsmentioning

confidence: 99%

Synthetic Cells and Molecules in Cellular Immunotherapy

Lin,

Li,

Zhang

et al. 2024

Int. J. Biol. Sci.

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Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

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Section: Synthetic Receptors For Programing T Cellsmentioning

confidence: 99%

Synthetic Cells and Molecules in Cellular Immunotherapy

Lin,

Li,

Zhang

et al. 2024

Int. J. Biol. Sci.

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show abstract

“…TCR-T cells overexpressing c-Jun and targeting hepatocellular carcinoma could improve the survival of mice with tumor growth [124] . The fusion of the TRAF-binding motif from 4-1BB ICD at the C-terminal of CD3z could enhance the persistence and expansion of TCR-T cells both in vitro and in vivo [125] . The induced expression of IL-12 in the PDCD1 locus could enhance the function of NY-ESO-1-specific TCR-T cells and eliminate established tumors in a xenograft mouse model, with greater TCR-T cell expansion potential [126] .…”

Section: Strategies To Improve Tcr-t Cell Therapy Beyond Tcr Engineeringmentioning

confidence: 99%

The recent advancement of TCR-T cell therapies for cancer treatment

Zhao*,

Shao,

2024

ABBS

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Adoptive cell therapies involve infusing engineered immune cells into cancer patients to recognize and eliminate tumor cells. Adoptive cell therapy, as a form of living drug, has undergone explosive growth over the past decade. The recognition of tumor antigens by the T-cell receptor (TCR) is one of the natural mechanisms that the immune system used to eliminate tumor cells. TCR-T cell therapy, which involves introducing exogenous TCRs into patients' T cells, is a novel cell therapy strategy. TCR-T cell therapy can target the entire proteome of cancer cells. Engineering T cells with exogenous TCRs to help patients combat cancer has achieved success in clinical trials, particularly in treating solid tumors. In this review, we examine the progress of TCR-T cell therapy over the past five years. This includes the discovery of new tumor antigens, protein engineering techniques for TCR, reprogramming strategies for TCR-T cell therapy, clinical studies on TCR-T cell therapy, and the advancement of TCR-T cell therapy in China. We also propose several potential directions for the future development of TCR-T cell therapy.

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Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

Ye,

Sun,

et al. 2024

Journal of Pharmaceutical Analysis

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Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into theCD247locus

Cited by 3 publications

References 58 publications

Synthetic Cells and Molecules in Cellular Immunotherapy

Synthetic Cells and Molecules in Cellular Immunotherapy

The recent advancement of TCR-T cell therapies for cancer treatment

Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

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