TCR γ4δ1-Engineered αβT Cells Exhibit Effective Antitumor Activity

He, Kangxia; You, Hongqin; Li, Yuxia; Cui, Lianxian; Zhang, Jianmin; Wang, He

doi:10.2119/molmed.2016.00023

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…We amplified full-length TCRδ1 with GTM sequence from cDNAs of gastric cancer tissues and TCRγ4 chains from cDNAs of gastric tumor-derived γδ TILs, which were then cloned into pREP9 and pREP7 vectors for sequence analysis. We found that TCRγ4δ1-engineered αβT cells exhibited significant cytotoxicity against HepG2 and BGC-803 tumor cells and were validated on mouse tumor models [89].…”

Section: Therapeutic Opportunities Brought By Tumor-associated Protei...mentioning

confidence: 84%

Tumor-associated protein ligands recognized by human γδ T cell receptor and their implications in cancer therapy

Liu

Zhang

et al. 2022

Explor Immunol

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In recent years, immunologists have been working to utilize the functional mechanism of the immune system to research new tumor treatment methods and achieved a major breakthrough in 2013, which was listed as one of the top 10 scientific breakthroughs of 2013 by Science magazine (see “Cancer immunotherapy”. Science. 2013;342:1417. doi: 10.1126/science.1249481). Currently, two main methods are used in clinical tumor immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Clinical responses to checkpoint inhibitors rely on blockade of the target neoantigens expressed on the surfaces of tumor cells, which can inhibit T cell activity and prevent the T cell immune response; therefore, the therapeutic effect is limited by the tumor antigen expression level. While CAR-T cell therapy can partly enhance neoantigen recognition of T cells, problems remain in the current treatment for solid tumors, such as restricted transport of adoptively transferred cells to the tumor site and off-targets. Immunologists have therefore turned their attention to γδ T cells, which are not restricted by the major histocompatibility complex (MHC) for neoantigen recognition and are able to initiate a rapid immune response at an early stage. However, due to the lack of an understanding of the antigens that γδ T cells recognize, the role of γδ T cells in tumorigenesis and tumor development is not clearly understood. In the past few years, extensive data identifying antigen ligands recognized by γδ T cells have been obtained, mainly focusing on bisphosphonates and small-molecule polypeptides, but few studies have focused on protein ligands recognized by γδ T cells. In this paper, it is reviewed and analyzed that the tumor-associated protein ligands of γδ T cells that have been discovered thus far, hoping to provide new ideas for the comprehensive application of γδ T cells in tumor immunotherapy.

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Section: Therapeutic Opportunities Brought By Tumor-associated Protei...mentioning

confidence: 84%

Tumor-associated protein ligands recognized by human γδ T cell receptor and their implications in cancer therapy

Liu

Zhang

et al. 2022

Explor Immunol

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“…The proliferation of γδT cells was detected by CellTrace™ CFSE Cell Proliferation Kit (Invitrogen™, Thermo Fisher, USA) as described previously (21, 22). In brief, γδT cells were amplified in vitro with anti-TCR PAN γ/δ monoclonal antibody (Beckman Coulter, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Identification of the Ligands of TCRγδ by Screening the Immune Repertoire of γδT Cells From Patients With Tuberculosis

Wang

Teng

et al. 2019

Front. Immunol.

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. γδT cells, which are characterized by major histocompatibility complex (MHC) non-restriction, are rapidly activated and initiate anti-infectious immune responses in the early stages of Mtb infection. However, the mechanism underlying the recognition of Mtb by γδT cells remains unclear. In this study, we characterized the pattern of the human T-cell receptor (TCR) γδ complementary determinant region 3 (CDR3) repertoire in TB patients by using high-throughput immune repertoire sequencing. The results showed that the diversity of CDR3δ was significantly reduced and that the frequency of different gene fragments (V/J), particularly the V-segment of the δ-chain, was substantially altered, which indicate that TB infection-related γδT cells, especially the δ genes, were activated and amplified in TB patients. Then, we screened the Mtb-associated epitopes/proteins recognized by γδT cells using an Mtb proteome chip with dominant CDR3δ peptides as probes. We identified the Mtb protein Rv0002 as a potential ligand capable of stimulating the activation and proliferation of γδT cells. Our findings provide a further understanding of the mechanisms underlying γδT cell-mediated immunity against Mtb infection.

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“…Surprisingly, endogenous ab TCRs were downregulated after the transduction of gd TCRs, leading to a lack of alloreactive response (147). Besides, several types of tumor specific CDR3d-grafted gd TCRs were also used to modify ab T cells and exhibited significant antitumor effects (148,149). Moreover, a novel antibody-TCR (Ab-TCR) modified ab T cells, combining Fabbased antigen recognition with gd TCR signaling, showed a similar cytotoxicity and a less cytokine release comparing with CD28/CD3z CAR-T cells (150).…”

Section: Gd Tcrs Transfer To Ab T Cellsmentioning

confidence: 99%

Engineering γδ T Cells: Recognizing and Activating on Their Own Way

et al. 2022

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Adoptive cell therapy (ACT) with engineered T cells has emerged as a promising strategy for the treatment of malignant tumors. Among them, there is great interest in engineered γδ T cells for ACT. With both adaptive and innate immune characteristics, γδ T cells can be activated by γδ TCRs to recognize antigens in a MHC-independent manner, or by NK receptors to recognize stress-induced molecules. The dual recognition system enables γδ T cells with unique activation and cytotoxicity profiles, which should be considered for the design of engineered γδ T cells. However, the current designs of engineered γδ T cells mostly follow the strategies that used in αβ T cells, but not making good use of the specific characteristics of γδ T cells. Therefore, it is no surprising that current engineered γδ T cells in preclinical or clinical trials have limited efficacy. In this review, we summarized the patterns of antigen recognition of γδ T cells and the features of signaling pathways for the functions of γδ T cells. This review will additionally discuss current progress in engineered γδ T cells and provide insights in the design of engineered γδ T cells based on their specific characteristics.

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TCR γ4δ1-Engineered αβT Cells Exhibit Effective Antitumor Activity

Cited by 5 publications

References 49 publications

Tumor-associated protein ligands recognized by human γδ T cell receptor and their implications in cancer therapy

Tumor-associated protein ligands recognized by human γδ T cell receptor and their implications in cancer therapy

Identification of the Ligands of TCRγδ by Screening the Immune Repertoire of γδT Cells From Patients With Tuberculosis

Engineering γδ T Cells: Recognizing and Activating on Their Own Way

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