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1. C-JUN overexpressing CAR-T cells in acute myeloid leukemia: preclinical characterization and phase I trial

Author

Zuo, Shiyu, Li, Chuo, Sun, Xiaolei, Deng, Biping, Zhang, Yibing, Han, Yajing, Ling, Zhuojun, Xu, Jinlong, Duan, Jiajia, Wang, Zelin, Yu, Xinjian, Zheng, Qinlong, Xu, Xiuwen, Zong, Jiao, Tian, Zhenglong, Shan, Lingling, Tang, Kaiting, Huang, Huifang, Song, Yanzhi, Niu, Qing, Zhou, Dongming, Feng, Sizhou, Han, Zhongchao, Wang, Guoling, Wu, Tong, Pan, Jing, and Feng, Xiaoming

Published
2024
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4. Autologous CD7 CAR-T cells generated without T cell pre-selection in pediatric patients with relapsed/refractory T-ALL: A phase I trial

Author

Zhao, Liping, Li, Chuo, Zuo, Shiyu, Han, Yajing, Deng, Biping, Ling, Zhuojun, Zhang, Yanlei, Peng, Shuixiu, Xu, Jinlong, Duan, Jiajia, Wang, Zelin, Yu, Xinjian, Zheng, Qinlong, Xu, Xiuwen, Yuan, Ying, Tian, Zhenglong, Tang, Kaiting, Zhang, Yibing, Niu, Qing, Zhang, Jiecheng, Chang, Alex H., Luo, Yuechen, Feng, Xiaoming, and Pan, Jing

Published
2024
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5. Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study

Author

Pan, Jing, Tang, Kaiting, Luo, Yuechen, Seery, Samuel, Tan, Yue, Deng, Biping, Liu, Feng, Xu, Xiuwen, Ling, Zhuojun, Song, Weiliang, Xu, Jinlong, Duan, Jiajia, Wang, Zelin, Li, Chunyu, Wang, Kai, Zhang, Yibing, Yu, Xinjian, Zheng, Qinlong, Zhao, Liping, Zhang, Jiecheng, Chang, Alex H, and Feng, Xiaoming

Published
2023
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11. CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia

Author

Pan, Jing, Niu, Qing, Deng, Biping, Liu, Shuangyou, Wu, Tong, Gao, Zhiyong, Liu, Zhaoli, Zhang, Yue, Qu, Xiaomin, Zhang, Yanlei, Liu, Shaohui, Ling, Zhuojun, Lin, Yuehui, Zhao, Yongqiang, Song, Yanzhi, Tan, Xiyou, Zhang, Yan, Li, Zhihui, Yin, Zhichao, Chen, Bingzhen, Yu, Xinjian, Yan, Ju, Zheng, Qinlong, Zhou, Xuan, Gao, Jin, Chang, Alex H., Feng, Xiaoming, and Tong, Chunrong

Published
2019
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14. Additional file 1 of Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia

Author

Tan, Yue, Shan, Lingling, Zhao, Liping, Deng, Biping, Ling, Zhuojun, Zhang, Yanlei, Peng, Shuixiu, Xu, Jinlong, Duan, Jiajia, Wang, Zelin, Yu, Xinjian, Zheng, Qinlong, Xu, Xiuwen, Tian, Zhenglong, Zhang, Yibing, Zhang, Jiecheng, Chang, Alex H., Feng, Xiaoming, and Pan, Jing

Abstract

Additional file 1. Materials and Methods. Fig. S1. Severe GVHD associated with higher LDH and ferritin in blood. Fig. S2. The incidence and persistance of GVHD according to the degree of HLA matching. A Early GVHD in patients receiving haploidentical donor cells and matched unrelated donor or matched sibling donor cells (MUD/MSD). B Late-onset GVHD in patients receiving haploidentical donor cells and matched unrelated donor or matched sibling donor cells (MUD/MSD). C Persistence of early GVHD between patients receiving haploidentical donor cells and MUD/MSD cells. D Persistence of late-onset GVHD between patients receiving haploidentical donor cells and MUD/MSD cells. Fig. S3. EBV and CMV viral load in the plasma. A Copy numbers of CMV DNA in plasma of individual patients. B Copy numbers of EBV DNA in plasma of individual patients. Fig. S4. Kaplan-Meier curves of duration of response after CD7 CAR T-cell therapy. A Kaplan-Meier curves of duration of response in all responded patients after CD7 CAR T-cell therapy. B Kaplan-Meier curves of duration of response in subgroups according to SCT after CD7 CAR T-cell therapy. Fig. S5. Representative staining of T, NK and NKT cells in the peripheral blood of a patient. Fig. S6. CD4+ and CD8+ T cell ratio in the peripheral blood of all patients. Fig. S7. Characterization of CD7- T cells from patients post CD7 CAR T-cell therapy. A CD45RA, CD62L and CD95 expression on CD4+ and CD8+ T cells from E018 at month 20 post CD7 CAR T-cell therapy and a healthy donor, as determined by flow cytometry. B T cell receptor (TCR) sequencing data, including the sum of the sequencing reads, TCR clones reconstructing from the sequencing reads and shannon entropy as an index of TCR Vβ usage diversity from indicated patients and healthy donors. C The number of T cells secreting IFN-γ in PBMCs from indicated patients, and healthy donors, after stimulation with phytohemagglutinin (PHA, as positive control), cytomegalovirus (CMV) or Epstein-Barr virus (EBV) peptide, as determined by IFN-γ ELISPOT assay. Table S1. Adverse events of special interest in all 20 treated patients and by subgroups. Table S2. The degree of HLA matching and GVHD. Table S3. Chimerism status after CAR T-cell infusion in all 20 treated patients.

Published
2023
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15. Profiles of Germline Predisposition Gene Variants in Hematologic Disorders and Its Impact on Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation

Author

Li, Zhihui, primary, Yang, Keyan, additional, Zheng, Qinlong, additional, Wang, Xianxuan, additional, Wu, Fan, additional, Li, Jing, additional, Wen, Xiaopei, additional, Zhang, Caiyan, additional, Wang, Jingjing, additional, Song, Yanzhi, additional, Zhao, Yongqiang, additional, and Wu, Tong, additional

Published
2022
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17. Genetic landscapes and curative effect of CAR T-cell immunotherapy in relapse and refractory DLBCL patients

Author

shi, hui, primary, zheng, peihao, additional, liu, rui, additional, xu, teng, additional, yang, fan, additional, feng, shaomei, additional, guo, yuelu, additional, ma, lixia, additional, liu, haidi, additional, lei, yang, additional, li, ruiting, additional, deng, biping, additional, hou, shuling, additional, li, yang, additional, Zheng, Qinlong, additional, HU, KAI, additional, and ke, xiaoyan, additional

Published
2022
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18. Efficacy and Safety of Sequential Different B Cell Antigen-Targeted CAR T-Cell Therapy for Pediatric Refractory/Relapsed Burkitt Lymphoma with Secondary Central Nervous System Involvement

Author

Liu, Ying, primary, Deng, Biping, additional, Hu, Bo, additional, Zhang, Wenqun, additional, Zhu, Qing, additional, Liu, Yang, additional, Wang, Shan, additional, Zhang, Pei, additional, Yang, Junhan, additional, Zheng, Qinlong, additional, Yu, Xinjian, additional, Gao, Zifen, additional, Zhou, Chunju, additional, Han, Wei, additional, Chang, Alex Hong, additional, and Zhang, Yonghong, additional

Published
2021
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21. ALK Inhibitor Plus Vinblasitine for Refractory/Relapsed Pediatric ALK+ Anaplastic Large Cell Lymphoma: A Prospective, One-Arm, Open-Label Real-World Study

Author

Zhang, Wenqun, primary, Wang, Shan, additional, Yang, Jing, additional, Hu, Bo, additional, Liu, Ying, additional, Jing, Ling, additional, Zhu, Qing, additional, Liu, Yang, additional, Zheng, Qinlong, additional, Zhou, Chunju, additional, Gao, Zifen, additional, and Zhang, Yonghong, additional

Published
2021
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22. Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial

Author

Pan, Jing, primary, Tan, Yue, additional, Wang, Guoling, additional, Deng, Biping, additional, Ling, Zhuojun, additional, Song, Weiliang, additional, Seery, Samuel, additional, Zhang, Yanlei, additional, Peng, Shuixiu, additional, Xu, Jinlong, additional, Duan, Jiajia, additional, Wang, Zelin, additional, Yu, Xinjian, additional, Zheng, Qinlong, additional, Xu, Xiuwen, additional, Yuan, Ying, additional, Yan, Fangrong, additional, Tian, Zhenglong, additional, Tang, Kaiting, additional, Zhang, Jiecheng, additional, Chang, Alex H., additional, and Feng, Xiaoming, additional

Published
2021
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28. Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL

Author

Pan, Jing, primary, Zuo, Shiyu, additional, Deng, Biping, additional, Xu, Xiuwen, additional, Li, Chuo, additional, Zheng, Qinlong, additional, Ling, Zhuojun, additional, Song, Weiliang, additional, Xu, Jinlong, additional, Duan, Jiajia, additional, Wang, Zelin, additional, Yu, Xinjian, additional, Chang, Alex H., additional, Feng, Xiaoming, additional, and Tong, Chunrong, additional

Published
2020
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33. Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist

Author

Neutzsky-Wulff Anita V, Andreassen Kim V, Hjuler Sara T, Feigh Michael, Bay-Jensen Anne-Christine, Zheng Qinlong, Henriksen Kim, and Karsdal Morten A

Subjects
Neo-epitope, Biomarkers, Type II diabetes mellitus, β-cell death, BIPED classification, Patient segregation, Personalized treatment, Medicine
Abstract

Abstract Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c). Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass. As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths. Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.

Published
2012
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35. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

Author

Skjøt-Arkil Helene, Clausen Rikke E, Nguyen Quoc Hai, Wang Yaguo, Zheng Qinlong, Martinez Fernando J, Hogaboam Cory M, Han Meilan, Klickstein Lloyd B, Larsen Martin R, Nawrocki Arkadiusz, Leeming Diana J, and Karsdal Morten A

Subjects
Elastin, Extracellular matrix remodeling, Biochemical marker, Neoepitope, COPD, IPF, MMP, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. Methods Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). Results The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p Conclusions MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings.

Published
2012
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36. Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

Author

Vassiliadis Efstathios, Rasmussen Lars M, Byrjalsen Inger, Larsen Dorthe, Chaturvedi Rajiv, Hosbond Susanne, Saabye Lotte, Diederichsen Axel CP, Genovese Federica, Duffin Kevin L, Zheng Qinlong, Chen Xiaoliang, Leeming Diana J, Christiansen Claus, and Karsdal Morten A

Subjects
Titin, CVD, MMP-12, Cardiovascular, Acute myocardial infarction, Biomarker, Neoepitope, Medicine
Abstract

Abstract Background Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage. Methods A competitive ELISA was developed to specifically measure levels of the titin sequence 12670’ NVTVEARLIK 12679’, derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa). Results Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (±43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (±90.14)] (P Conclusions The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.

Published
2012
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37. Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

Author

Sondergaard Bodil-Cecilie, Madsen Suzi H, Karsdal Morten A, Jensen Anne-Christine, Chen Pingping, Wang Bijue, Zheng Qinlong, and Qvist Per

Subjects
Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Background Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. Findings Bovine cartilage explants were cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM) and tumor necrosis factor alpha (TNFα). In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo-epitope specific immunoassays; (1) sandwich 342FFGVG-G2 ELISA, (2) competition NITEGE373ELISA (3) sandwich G1-NITEGE373 ELISA (4) competition 374ARGSV ELISA, and (5) sandwich 374ARGSV-G2 ELISA all detecting aggrecan fragments, and (6) sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen. We found that (1) aggrecanase-derived aggrecan fragments are released in the early (day 2-7) and mid phase (day 9-14) into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2) the release of NITEGE373 neo-epitopes are delayed compared to the corresponding 374ARGSV fragments, (3) the MMP inhibitor GM6001 did not reduce the release of aggrecanase-derived fragment, but induced a further delay in the release of these fragments, and finally (4) the MMP-derived aggrecan and type II collagen fragments were released in the late phase (day 16-21) only. Conclusion Our data support the model, that aggrecanases and MMPs act independently in the processing of the aggrecan molecules, and furthermore that suppression of MMP-activity had little if any effect on the quantity of aggrecanase-derived fragments released from explants cultures.

Published
2009
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38. Clinical Implications of Germline Predisposition Gene Variants in Patients with Refractory or Relapsed B Acute Lymphoblastic Leukemia

Author

Defeng, Zhao, Wu, Tong, Tong, Chunrong, Yuehui, Lin, and Zheng, Qinlong

Abstract

Objectives:Gene variants are important factors in prognosis of the patients with hematological malignancies. In current study, our team investigate the relationship between blood and immune system germline predisposition variants and refractory/relapsed acute B lymphoblastic leukemia in patients.

Published
2023
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40. CD7 Chimeric Antigen Receptor T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation Remarkably Improved Long-Term Disease-Free Survival in Refractory/Relapsed T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Author

Li, Zhihui, Zheng, Qinlong, Yang, Keyan, Xu, Teng, Wang, Lei, Wang, Xianxuan, Wen, Xiaopei, Song, Yanzhi, Zhao, Yongqiang, and Wu, Tong

Abstract

Introduction:The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) is poor, and salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) can only result in 20%-30% disease-free survival (DFS). Our previous clinical trials have shown that the patients with r/r T-ALL have achieved 90% complete remission (CR) with CD7 chimeric antigen receptor T cell (CART) therapy (Pan J. et al. JCO 2021), then quick received allo-HSCT to obtain 57% of 1-year DFS in 12 patients (Li ZH. et al. Transplantation and Cellular Therapy 2022).

Published
2023
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42. A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Author

Barascuk, Natasha, Genovese, Federica, Larsen, Lise, Byrjalsen, Inger, Zheng, Qinlong, Sun, Shu, Hosbond, Susanne Elisabeth, Poulsen, Tina Svenstrup, Diederichsen, Axel Cosmus Pyndt, Jensen, Jesper Møller, Mickley, Hans, Register, Thomas C, Rasmussen, Lars M, Leeming, Diana Julie, and Karsdal, Morten A

Abstract

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current study was to develop an immunoassay to detect a specific MMP-12 derived versican degradation fragment (VCANM) and assess its potential as a biomarker for extracellular matrix remodelling in atherosclerosis. A mouse monoclonal antibody raised against VCANM was used for the development of a competitive ELISA for detection of the fragment in plasma. VCANM was measured in plasma of patients with different levels of heart diseases. Patients experiencing I) acute coronary syndrome, II) stable ischemic heart disease and III) demonstrating high levels of coronary calcium deposits had significantly higher plasma levels of VCANM compared to a control group of individuals with no detectable coronary calcium deposits. VCANM was also detected by immunohistochemistry in coronary artery sections of patients with different degrees of atherosclerosis. VCANM ability to separate patients with atherosclerotic diseases from healthy individuals suggested VCANM as a potential biomarker for the pathological arterial matrix remodelling associated with atherosclerosis.

Published
2013

45. Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation

Author

He, Yi, primary, Siebuhr, Anne Sofie, additional, Brandt-Hansen, Niels Ulrik, additional, Wang, Jianxia, additional, Su, Di, additional, Zheng, Qinlong, additional, Simonsen, Ole, additional, Petersen, Kristian Kjær, additional, Arendt-Nielsen, Lars, additional, Eskehave, Thomas, additional, Hoeck, Hans Christian, additional, Karsdal, Morten Asser, additional, and Bay-Jensen, Anne C, additional

Published
2014
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47. MMP Mediated Degradation of Type IV Collagen Alpha 1 and Alpha 3 Chains Reflects Basement Membrane Remodeling in Experimental and Clinical Fibrosis – Validation of Two Novel Biomarker Assays

Author

Sand, Jannie Marie, primary, Larsen, Lise, additional, Hogaboam, Cory, additional, Martinez, Fernando, additional, Han, MeiLan, additional, Røssel Larsen, Martin, additional, Nawrocki, Arkadiusz, additional, Zheng, Qinlong, additional, Asser Karsdal, Morten, additional, and Leeming, Diana Julie, additional

Published
2013
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48. Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

Author

Skjøt-Arkil, Helene, primary, Clausen, Rikke E., additional, Rasmussen, Lars M., additional, Wang, Wanchun, additional, Wang, Yaguo, additional, Zheng, Qinlong, additional, Mickley, Hans, additional, Saaby, Lotte, additional, Diederichsen, Axel C. P., additional, Lambrechtsen, Jess, additional, Martinez, Fernando J., additional, Hogaboam, Cory M., additional, Han, MeiLan, additional, Larsen, Martin R., additional, Nawrocki, Arkadiusz, additional, Vainer, Ben, additional, Krustrup, Dorrit, additional, Bjørling-Poulsen, Marina, additional, Karsdal, Morten A., additional, and Leeming, Diana J., additional

Published
2013
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49. An Enzyme-Generated Fragment of Tau Measured in Serum Shows an Inverse Correlation to Cognitive Function

Author

Henriksen, Kim, primary, Wang, Yaguo, additional, Sørensen, Mette G., additional, Barascuk, Natasha, additional, Suhy, Joyce, additional, Pedersen, Jan T., additional, Duffin, Kevin L., additional, Dean, Robert A., additional, Pajak, Monika, additional, Christiansen, Claus, additional, Zheng, Qinlong, additional, and Karsdal, Morten A., additional

Published
2013
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50. Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

Author

Genovese, Federica, primary, Barascuk, Natasha, additional, Larsen, Lise, additional, Larsen, Martin Røssel, additional, Nawrocki, Arkadiusz, additional, Li, Yili, additional, Zheng, Qinlong, additional, Wang, Jianxia, additional, Veidal, Sanne Skovgård, additional, Leeming, Diana Julie, additional, and Karsdal, Morten Asser, additional

Published
2013
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