Acute myeloid leukemia (AML) is the main type of leukemia, accounting for about 60% of all leukemia, with complex pathogenesis and great clinical heterogeneity. Effective targets for AML need to be further developed. We performed next-generation sequencing analysis of the TCR sequence of an AML patient to find the patient's specific TCR clone for leukemia. The rearranged TCR gene stimulated by leukemia antigens was transduced into the patient's own T cells, and the TCR gene-modified T cells (TCR-T) that could specifically recognize leukemia antigens and kill leukemia cells were constructed. Enhancing the specificity and killing activity of T cells can truly achieve individualized treatment for patients. In addition, through TCR sequencing, the TCR sequence database of leukemia patients can be constructed to find the common specific TCR clones for AML among different patients, which can realize the precise treatment of AML.

开始日期2019-01-01

申办/合作机构

Shenzhen University General Hospital

100 项与 TCR-T Cells(Shenzhen University General Hospital) 相关的临床结果

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100 项与 TCR-T Cells(Shenzhen University General Hospital) 相关的转化医学

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项与 TCR-T Cells(Shenzhen University General Hospital) 相关的文献（医药）

2025-01-28·Leukemia & Lymphoma

Adoptive cell therapy in acute myeloid leukemia: the current landscape and emerging strategies

Review

作者: Azzi, Jacques ; Tremblay, Douglas ; Tharakan, Serena

Efforts to produce adoptive cell therapies in AML have been largely unfruitful, despite the success seen in lymphoid malignancies. Identifying targetable antigens on leukemic cells that are absent on normal progenitor cells remains a major obstacle, as is the hostile tumor microenvironment created by AML blasts. In this review, we summarize the challenges in the development of adoptive cell therapies such as CAR-T, CAR-NK, and TCR-T cells in AML, discussing both autologous and allogeneic therapies. We also discuss methods to address myelotoxicity associated with these therapies, including rapidly switchable CAR platforms and CRISPR-Cas9 genetic engineering of hematopoietic stem cells. Finally, we present the current clinical landscape in these areas, along with future directions in the field.

2022-12-01·Experimental Hematology & Oncology

TCR engineered T cells for solid tumor immunotherapy

Review

作者: Li, Yangqiu ; Wei, Wei ; Liu, Zhipeng ; Zhang, Yikai

AbstractT cell immunotherapy remains an attractive approach for cancer immunotherapy. T cell immunotherapy mainly employs chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has been an essential breakthrough in treating hematological malignancies. TCR-T cells can recognize antigens expressed both on cell surfaces and in intracellular compartments. Although TCR-T cells have not been approved for clinical application, a number of clinical trials have been performed, particularly for solid tumors. In this article, we summarized current TCR-T cell advances and their potential advantages for solid tumor immunotherapy.

2018-08-01·Hepatology1区 · 医学

Identification of α‐fetoprotein‐specific T‐cell receptors for hepatocellular carcinoma immunotherapy

1区 · 医学

Article

作者: Wang, Lan ; He, Yukai ; Kruse, Edward ; Hong, Yuan ; Huang, Lei ; Peng, Yibing ; Wu, Juan ; Zhu, Wei ; Liu, Heping ; Merchen, Todd ; Jiang, Xiaotao ; Li, Qi ; Celis, Esteban

Hepatocellular carcinoma (HCC) is the major form of liver cancer for which there is no effective therapy. Genetic modification with T‐cell receptors (TCRs) specific for HCC‐associated antigens, such as α‐fetoprotein (AFP), can potentially redirect human T cells to specifically recognize and kill HCC tumor cells to achieve antitumor effects. In this study, using lentivector and peptide immunization, we identified a population of cluster of differentiation 8 (CD8) T cells in human leukocyte antigen (HLA)‐A2 transgenic AAD mice that recognized AFP158 epitope on human HCC cells. Adoptive transfer of the AFP158‐specific mouse CD8 T cells eradicated HepG2 tumor xenografts as large as 2 cm in diameter in immunocompromised nonobese diabetic severe combined immunodeficient gamma knockout (NSG) mice. We then established T‐cell hybridoma clones from the AFP158‐specific mouse CD8 T cells and identified three sets of paired TCR genes out of five hybridomas. Expression of the murine TCR genes redirected primary human T cells to bind HLA‐A2/AFP158 tetramer. TCR gene‐engineered human T (TCR‐T) cells also specifically recognized HLA‐A2+AFP+ HepG2 HCC tumor cells and produced effector cytokines. Importantly, the TCR‐T cells could specifically kill HLA‐A2+AFP+ HepG2 tumor cells without significant toxicity to normal primary hepatocytes in vitro. Adoptive transfer of the AFP‐specific TCR‐T cells could eradicate HepG2 tumors in NSG mice. Conclusion: We have identified AFP‐specific murine TCR genes that can redirect human T cells to specifically recognize and kill HCC tumor cells, and those AFP158‐specific TCRs have a great potential to engineer a patient's autologous T cells to treat HCC tumors. (Hepatology 2018).

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