Generation of V α13/β21+T cell specific target CML cells by TCR gene transfer

Zha, Xianfeng; Xu, Ling; Chen, Shaohua; Yang, Lijian; Zhang, Yikai; Lu, Yuhong; Yu, Zhi; Li, Bo; Wu, Xiuli; Zheng, Wenjie; Li, Yangqiu

doi:10.18632/oncotarget.12441

Cited by 9 publications

(10 citation statements)

References 51 publications

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“…To construct TCR-modified T cells, the isolation of TCRs that specifically recognize leukemia-specific antigen (LSA) or leukemia-associated antigen (LAA) epitopes is the first step. The TCRs could be identified in T cell clones possessing potent activity against leukemia cells either from the blood or bone marrow of leukemia patients [11] or from healthy donor T cells induced by LSA or LAA peptides with major histocompatibility complex (MHC) class-I/II-restriction. For example, WT1 is constitutively expressed in myeloid leukemia cells, including acute myelocytic leukemia (AML) and CML, and myelodysplastic syndrome (MDS), and WT1-specific CTLs have been identified in blood from leukemia patients [12, 13].…”

Section: Identification Of Leukemia-specific Tcrsmentioning

confidence: 99%

T cell receptor-engineered T cells for leukemia immunotherapy

Zhang

2019

Cancer Cell Int

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At present, refractory and relapse are major issues for leukemia therapy and a major cause of allogeneic hematopoietic stem cell transplant failure. Over the last decade, many studies have demonstrated that adoptive cancer antigen-specific T cell therapy is an effective option for leukemia therapy. Recently, T cell immunotherapy studies have mainly focused on chimeric antigen receptor- and T cell receptor-engineered T cells. Clinical trials involving chimeric antigen receptor-engineered T cells have been a major breakthrough and became a novel therapy for leukemia. As another potential therapy for leukemia, clinical application of TCR-engineered T cells remains in its infancy. This article presents a review of the current status of anti-leukemia immunotherapy using leukemia antigen-specific TCR-engineered T cells.

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Section: Identification Of Leukemia-specific Tcrsmentioning

confidence: 99%

T cell receptor-engineered T cells for leukemia immunotherapy

Zhang

2019

Cancer Cell Int

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“…17,[22][23][24] Clonally expanded TCR + T cells were identified in patients with hematologic malignancies and cancer, and the identified tumor antigen-specific TCR gene could be used to construct TCR-modified T cells (TCR-T) for cancer immunotherapy. 2,[25][26][27] Molecular analysis, particularly using next-generation sequencing and single-cell sequencing, could identify clonal TCR rearrangements, confirming specifically expanded T cell clones and monitoring antigen-specific T cell responses, which may help to design effective TCR-based immunotherapies. [28][29][30] However, these analyses are incapable of evaluating the functional status of clonally expanded T cells.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown an altered distribution of TCRα and TCRβ repertoire in cancer and leukemia patients at the molecular level by TCR rearrangement analysis . Clonally expanded TCRαβ+ T cells were identified in patients with hematologic malignancies and cancer, and the identified tumor antigen‐specific TCRαβ gene could be used to construct TCR‐modified T cells (TCR‐T) for cancer immunotherapy . Molecular analysis, particularly using next‐generation sequencing and single‐cell sequencing, could identify clonal TCR rearrangements, confirming specifically expanded T cell clones and monitoring antigen‐specific T cell responses, which may help to design effective TCR‐based immunotherapies .…”

Section: Introductionmentioning

confidence: 99%

A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia

Huang

Tan

Chen

et al. 2019

Journal of Leukocyte Biology

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The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global T cell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR Vβ subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+T cells were increased in AML, particularly TCR Vβ2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death‐1 (PD‐1)+T cells in TCR Vβ subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD‐1+Vβ+T cells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD‐1+Vβ2+T cells with a high number of Vβ2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD‐1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+T cells were distributed in the AML‐M5 subtype group compared with the AML‐M3 group. In addition, higher PD‐1+ Vβ5.2+ and PD‐1+ Vβ12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD‐1+Vβ+T cells is a common characteristic of AML, higher PD‐1+Vβ2+T cells may be associated with a low antileukemia effect, and higher PD‐1+Vβ5.2+ and PD‐1+Vβ12+CD8+T cells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.

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“…Graft- versus -leukemia effects have been proven to have the power to eliminate minimal residual disease (MRD) in the setting of allogeneic stem cell transplantation (allo-SCT) and donor lymphocytes infusion (DLI) [ 1 - 3 ]. Other immunotherapeutic strategies under investigation include vaccination and adoptive T cell transfer, which have had some exciting results [ 3 - 5 ], but initial trial data have been disappointing [ 6 ]. Leukemia cells and the leukemia cell-induced immune suppressive microenvironment are likely to be responsible for failure in these immunotherapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment

Yao

Tan

et al. 2017

Oncotarget

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T cell immune surveillance is considered an important host protection process for inhibiting carcinogenesis. The full capacity of T cell immune surveillance is dependent on T cell homeostasis, particularly for central memory T (TCM) cells and stem cell memory T (TSCM) cells. In this study, distribution of T cell subsets in peripheral blood from 12 patients with chronic myeloid leukemia (CML) and 12 cases with CML in complete remission (CR) was analyzed using a multicolor flow cytometer, and 16 samples from healthy individuals (HIs) served as control. The proportion of CD8+ TSCM and CD4+ and CD8+ TCM cells were lower, while CD4+ effector memory T (TEM) cells and CD4+ and CD8+ terminal effector T (TEF) cells were higher in CML patients compared with HIs. Moreover, the proportion of CD8+CD28- T cells, which were found to have the immune suppressive function, increased in the naive T (TN) cell and TCM subsets in CML patients compared with HIs. Our study reveals that elimination of leukemia cells by treating with tyrosine kinase inhibitors (TKIs) restores the memory T cell distribution from a skewed pattern in CML patients who are under leukemia burden, indicating that leukemia-specific immune responses mediated by T cells might be induced and maintained in CML patients, however, these responsive T cells might gradually become exhausted due to the continued existence of leukemia cells and their environment; therefore, T cell activation using a different approach remains a key point for enhancing global T cell immunity in CML patients, even for those with CR status.

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Generation of V α13/β21+T cell specific target CML cells by TCR gene transfer

Cited by 9 publications

References 51 publications

T cell receptor-engineered T cells for leukemia immunotherapy

T cell receptor-engineered T cells for leukemia immunotherapy

A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia

Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment

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