Yingxi Xu

Institute of Hematology & Blood Diseases Hospital

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Qing Rao

Institute of Hematology & Blood Diseases Hospital

Jianxiang Wang

Institute of Hematology & Blood Diseases Hospital

Haiyan Xing

Institute of Hematology & Blood Diseases Hospital

Tian Zheng

Columbia University

Min Wang

Chinese Academy of Medical Sciences & Peking Union Medical College

Kejing Tang

The First Affiliated Hospital, Sun Yat-sen University

Shaowei Qiu

Chinese Academy of Medical Sciences & Peking Union Medical College

Runxia Gu

Institute of Hematology & Blood Diseases Hospital

Junli Mou

Chinese Academy of Medical Sciences & Peking Union Medical College

Ying Wang

First Affiliated Hospital of Xi'an Jiaotong University

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Chinese Academy of Medical Sciences & Peking Union Medical College

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Institute of Hematology & Blood Diseases Hospital

128

China Medical University

Sun Yat-sen University

Nankai University

Chinese Academy of Sciences

Sichuan University

Shanghai Jiao Tong University

Capital Medical University

Peking Union Medical College Hospital

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Correction: Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

Blood Cancer Journal (2022)

Nianci Chen Yingxi Xu Junli Mou Qing Rao Haiyan Xing

10.1038/s41408-022-00627-3

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Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells

Journal of Hematology & Oncology (2018)

Ying Wang Yingxi Xu Saisai Li Jia Liu Yanyan Xing

Chimeric antigen receptor-engineered T (CAR-T) cells have extraordinary effect in treating lymphoblastic leukemia. However, treatment of acute myeloid leukemia (AML) using CAR-T cells remains limited to date. Leukemogenesis always relates with the abnormalities of cytogenetics, and nearly one third of AML patients have activating mutations in Fms-like tyrosine kinase 3 (FLT3) which reminded poor prognosis. Considering the FLT3 expressed in AML patients' blast cells, it may be a new candidate target for CAR-T therapy to treat FLT3+ AML, especially patients harboring FLT3-ITD mutation. The FLT3L CAR-T using FLT3 ligand as recognizing domain was constructed. The specific cytotoxicity against FLT3+ leukemia cell lines, primary AML cells, and normal hematopoietic progenitor stem cells (HPSCs) in vitro were evaluated. In addition, FLT3+ AML mouse model was used to assess the effect of FLT3L CAR-T therapy in vivo. FLT3L CAR-T cells could specifically kill FLT3+ leukemia cell lines and AML patients' bone marrow mononuclear cells in vitro (with or without FLT3 mutation) and have more potent cytotoxicity to FLT3-ITD cells. In a human FLT3+ AML xenograft mouse model, FLT3L CAR-T cells could significantly prolong the survival of mice. Furthermore, it was found that FLT3L CAR-T cells could activate the FLT3/ERK signaling pathway of FLT3+ leukemia cells with wild-type FLT3; meanwhile, it had no inhibitory effects on the colony formation of CD34+ stem cells derived from normal human umbilical cord blood. The ligand-based FLT3L CAR-T cells could be a promising strategy for FLT3+ AML treatment, especially those carried FLT3 mutation.

Hematology

10.1186/s13045-018-0603-7

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Citations (95)

Single-cell transcriptome of early hematopoiesis guides arterial endothelial-enhanced functional T cell generation from human PSCs

Science Advances (2021)

Jun Shen Yingxi Xu Shuo Zhang Shuzhen Lyu Yingying Huo

Hypoxia enhances hematopoiesis with functional T cell potential from human pluripotent stem cells via arterial priming.

10.1126/sciadv.abi9787

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Citations (19)

Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T/CAR-T Cells

Human Gene Therapy (2023)

Leling Xie Runxia Gu Xue Yang Shaowei Qiu Yingxi Xu

Chimeric antigen receptor T (CAR-T) cell therapy initiates new methods and turns the scale of clinical treatment on relapsed/refractory acute T lymphoblastic leukemia (T-ALL). In this study, we generated the second-generation CD7-targeting CAR-T cells with a new antigen-binding single-chain variable fragment sequence and made it universal via CRISPR-based knockout of

Jurkat cells

10.1089/hum.2023.029

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Anti-tumor effects of vascular endothelial growth factor/vascular endothelial growth factor receptor binding domain-modified chimeric antigen receptor T cells

Cytotherapy (2021)

Haiyan Xing Xue Yang Yingxi Xu Kejing Tang Tian Zheng

Lymphangiogenesis

10.1016/j.jcyt.2021.05.008

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Citations (21)

Phosphorylation of Tip60 by p38α regulates p53-mediated PUMA induction and apoptosis in response to DNA damage

Oncotarget (2014)

Yingxi Xu Rong Liao Na Li Rong Xiang Peiqing Sun

// Yingxi Xu 1, 2 , Rong Liao 2 , Na Li 1 , Rong Xiang 1 , Peiqing Sun 2 1 College of Medicine, Nankai University, Tianjin, P.R. China, 300071 2 Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 Correspondence to: Peiqing Sun, e-mail: pqsun@scripps.edu Rong Xiang, e-mail: rxiang@nankai.edu.cn Keywords: p38, Tip60, p53, PUMA, apoptosis Received: September 16, 2014 Accepted: November 08, 2014 Published: December 10, 2014 ABSTRACT Tip60 is a multifunctional acetyltransferase involved in multiple cellular functions. Acetylation of p53 at K120 by Tip60 promotes p53-mediated apoptosis after DNA damage. We previous showed that Tip60 activity is induced by phosphorylation at T158 by p38. In this study, we investigated the role of p38-mediated Tip60 phosphorylation in p53-mediated, DNA damage-induced apoptosis. We found that DNA damage induces p38 activation, Tip60-T158 phosphorylation, and p53-K120 acetylation with similar kinetics. p38α is essential for DNA damage-induced Tip60-T158 phosphorylation. In addition, both p38α and Tip60 are essential for p53-K120 acetylation, binding of p53 to PUMA promoter, PUMA expression and apoptosis induced by DNA damage. Moreover, DNA damage induces protein kinase activity of p38α towards Tip60-T158, and constitutive activation of p38 in cells leads to increases in Tip60-T158 phosphorylation, p53-K120 acetylation, PUMA expression and apoptosis. Furthermore, the Tip60-T158A mutant that cannot be phosphorylated by p38 fails to mediate p53-K120 acetylation, PUMA induction, and apoptosis following DNA damage. These results establish that Tip60-T158 phosphorylation by p38 plays an essential role in stimulating Tip60 activity required for inducing the p53-PUMA pathway that ultimately leads to apoptosis in response to DNA damage, which provides a mechanistic basis for the tumor-suppressing function of p38 and Tip60.

Puma

10.18632/oncotarget.2717

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Citations (20)

ZFP36L2, a novel AML1 target gene, induces AML cells apoptosis and inhibits cell proliferation

Leukemia Research (2018)

Jia Liu Wenting Lu Shuang Liu Ying Wang Saisai Li

Phenylbutyrate

Histone deacetylase inhibitor

10.1016/j.leukres.2018.02.017

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Citations (18)

Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19+ malignancy in a mouse model

Cytotherapy (2020)

Qian Liu Yingxi Xu Junli Mou Kejing Tang Xuehang Fu

NK-92

10.1016/j.jcyt.2020.06.003

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Citations (36)

Single-Cell Transcriptome of Early Hematopoiesis Guides Arterial Endothelium-Promoted Functional T Cell Generation from Human Pluripotent Stem Cells

Blood (2020)

Jun Shen Yingxi Xu Shuo Zhang Shuzhen Lyu Zack Wang

10.1182/blood-2020-140609

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[Functional investigation of chimeric antigen receptor T cells targeting LMP1 antigen].

PubMed (2022)

Huan He Yanyan Xing Yumin Zhang Yingxi Xu Tian Zheng

Objective: This study aimed to create a type of CAR-T cells that targets LMP1 antigen and study its immunotherapeutic effect on LMP1-positive hematological malignancies. Methods: To generate LMP1 CAR-T cells, a plasmid expressing LMP1 CAR was created using molecular cloning technology, and T cells were infected with LMP1 CAR lentivirus. The effects of LMP1 CAR-T cells on specific cytotoxicity against LMP1-positive tumor cell lines infected with the EB virus had been confirmed. Results: ① LMP1 protein expressing on EB virus-positive lymphoma cells surface was verified. ② The LMP1 CAR-expressing plasmid was created, and LMP1 CAR-T cells were obtained by infecting T cells with a lentivirus packaging system, with an infection efficiency of more than 80% . ③LMP1 CAR-T cells have a 4∶1 effect-to-target ratio in killing LMP1-positive lymphoma cells. The killing effect of LMP1 CAR-T cells on Raji cells was enhanced after 48 h of coculture, but there was no significant killing effect on Ramos, which are LMP1-negative lymphoma cells. ④After coculture with LMP1-positive lymphoma cells at a ratio of 1∶1 for 5 h, the degranulation effect was enhanced. The proportion of CD107a(+) T cells in the LMP1 CAR-T cell treatment group was significantly higher than that in the vector-T cell group [ (13.25±2.94) % vs (1.55±0.05) % , t=3.972, P=0.017]. ⑤After coculture with LMP1-positive lymphoma cells, the proportion of CD69(+) and CD25(+) T cells in the LMP1 CAR-T cell group was significantly higher than that in vector-T cell group [ (7.40±0.41) % vs (3.48±0.47) % , t=6.268, P=0.003; (73.00±4.73) % vs (57.67±2.60) % , t=2.842, P=0.047]. ⑥After coculture with LMP1-positive lymphoma cells, cytokine secretion in the LMP1 CAR-T cell group was higher than that in the vector-T cell group [interferon-gamma: (703±73) ng/L vs (422±87) ng/L, t=2.478, P=0.068; tumor necrosis factor-alpha: (215±35) ng/L vs (125±2) ng/L, t=2.536, P=0.064]. Conclusion: In this study, we found that the LMP1 protein is only found on the surface of the EBV-positive tumor cell. Simultaneously, we created an LMP1 CAR-expressing plasmid and obtained LMP1 CAR-T cells by infecting T cells with a lentivirus packaging system. Furthermore, we demonstrated that LMP1 CAR-T cells could specifically kill LMP1-positive tumor cells in vitro. The degranulation and activation effects of LMP1 CAR-T cells were enhanced after coculture with LMP1-positive tumor cells, indicating a potential clinical application.目的：制备一种靶向LMP1抗原的嵌合抗原受体T细胞（CAR-T细胞），研究其对EB病毒（EBV）阳性淋巴瘤的免疫治疗作用。方法：应用分子克隆技术构建二代LMP1 CAR表达质粒，通过慢病毒包装体系包装病毒后感染人T细胞，获得LMP1 CAR-T细胞，体外实验验证LMP1 CAR-T细胞对感染EBV后的LMP1阳性淋巴瘤细胞的特异性细胞毒性作用。结果： ①LMP1蛋白表达于EBV阳性的淋巴瘤细胞表面；②成功构建了二代LMP1 CAR慢病毒载体，感染人T细胞，获取LMP1 CAR-T细胞，感染效率大于80%；③LMP1 CAR-T细胞可特异性杀伤LMP1阳性淋巴瘤细胞，当效靶比按4∶1共培养48 h后，LMP1 CAR-T细胞对Raji细胞的杀伤作用增强，对Ramos细胞无明显杀伤作用；④与LMP1阳性淋巴瘤细胞按1∶1共培养5 h后，LMP1 CAR-T细胞处理组CD107a(+) T细胞比例显著高于Vector-T细胞组[（13.25±2.94）%对（1.55±0.05）%，t＝3.972，P＝0.017]，脱颗粒效果增强；⑤与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞组CD69(+)、CD25(+) T细胞比例显高于Vector-T细胞组[（7.40±0.41）%对（3.48±0.47）%，t＝6.268，P＝0.003；（73.00±4.73）%对（57.67±2.60）%，t＝2.842，P＝0.047]，活化效应增强。⑥与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞组细胞因子分泌增强，高于Vector-T细胞组[IFN-γ：（703±73）ng/L对（422±87）ng/L，t＝2.478，P＝0.068；TNF-α：（215±35）ng/L对（125±2）ng/L，t＝2.536，P＝0.064]。结论：该研究证实EBV阳性淋巴瘤细胞表面可特异表达LMP1蛋白，成功构建了LMP1 CAR慢病毒载体并感染人T细胞，成功获得LMP1 CAR-T细胞。体外实验证实：与LMP1阳性淋巴瘤细胞共培养后，LMP1 CAR-T细胞脱颗粒效果增强，活化效应增强，高效分泌细胞因子，可特异杀伤LMP1阳性淋巴瘤细胞，具有潜在的临床应用前景。.

Raji cell

10.3760/cma.j.issn.0253-2727.2022.03.008

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Citations (1)