12 results on '"Gongqiang Wu"'
Search Results
2. CAR-T-Cell Therapy Based on Immune Checkpoint Modulation in the Treatment of Hematologic Malignancies
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Manqi Su, Zhanna Zhang, Panruo Jiang, Xiaoxia Wang, Xiangmin Tong, and Gongqiang Wu
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Medicine - Abstract
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary immunotherapy that has shown significant success in treating certain hematologic malignancies. However, there are still challenges and limitations associated with this therapy, and not all cancer patients benefit from this therapy alone. Therefore, modifying CAR-T-cell therapy based on immune checkpoints, and its combination with immune checkpoint inhibitors (ICIs), shows promise as a potentially more effective strategy for treating hematologic malignancies. This article outlines the progress of preclinical and clinical trials of CAR-T-cell therapy based on immune checkpoint modulation in the treatment of hematologic malignancies. more...
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- 2024
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Catalog
3. Unlocking Apoptotic Pathways: Overcoming Tumor Resistance in CAR‐T‐Cell Therapy
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Zhanna Zhang, Manqi Su, Panruo Jiang, Xiaoxia Wang, Xiangmin Tong, and Gongqiang Wu
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apoptotic pathways ,CAR‐T‐cell therapy resistance ,tumor ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ABSTRACT Background Chimeric antigen receptor (CAR)‐T‐cell therapy has transformed cancer treatment, leading to remarkable clinical outcomes. However, resistance continues to be a major obstacle, significantly limiting its efficacy in numerous patients. Objectives This review critically examines the challenges associated with CAR‐T‐cell therapy, with a particular focus on the role of apoptotic pathways in overcoming resistance. Methods We explore various strategies to sensitize tumor cells to CAR‐T‐cell‐mediated apoptosis, including the use of combination therapies with BH3 mimetics, Mcl‐1 inhibitors, IAP inhibitors, and HDAC inhibitors. These agents inhibit anti‐apoptotic proteins and activate intrinsic mitochondrial pathways, enhancing the susceptibility of tumor cells to apoptosis. Moreover, targeting the extrinsic pathway can increase the expression of death receptors on tumor cells, further promoting their apoptosis. The review also discusses the development of novel CAR constructs that enhance anti‐apoptotic protein expression, such as Bcl‐2, which may counteract CAR‐T cell exhaustion and improve antitumor efficacy. We assess the impact of the tumor microenvironment (TME) on CAR‐T cell function and propose dual‐targeting CAR‐T cells to simultaneously address both myeloid‐derived suppressor cells (MDSCs) and tumor cells. Furthermore, we explore the potential of combining agents like PPAR inhibitors to activate the cGAS‐STING pathway, thereby improving CAR‐T cell infiltration into the tumor. Conclusions This review highlights that enhancing tumor cell sensitivity to apoptosis and increasing CAR‐T cell cytotoxicity through apoptotic pathways could significantly improve therapeutic outcomes. Targeting apoptotic proteins, particularly those involved in the intrinsic mitochondrial pathway, constitutes a novel approach to overcoming resistance. The insights presented herein lay a robust foundation for future research and clinical applications aimed at optimizing CAR‐T cell therapies. more...
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- 2024
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4. Targeted therapy for leukemia based on nanomaterials
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Suying Qian, Cuiping Zheng, Yanfang Wu, Huiyan Huang, Gongqiang Wu, and Junyu Zhang
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Leukemia ,Targeted therapy ,Nanomaterials ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Leukemia is a kind of hematopoietic stem cell malignant clonal disease. Drug therapy is the core treatment strategy for leukemia, but the current therapeutic drugs have defects such as low bioavailability, large adverse reactions and inconvenient intravenous administration. Targeted therapy can combine drugs with specific carcinogenic sites on cells to kill cancer cells and avoid damage to normal cells, which has gradually become the mainstream method of leukemia treatment. In addition, nanomedicine delivery systems can significantly improve drug efficacy through controlled size and targeted optimization of drug delivery by modification strategies. Therefore, the targeted treatment of leukemia based on nanomaterials has great research value and application prospect. This paper gives an overview of the current therapeutic strategies for leukemia, and then reviews the cutting-edge targeted therapeutic nanomaterials for leukemia, including organic nanomaterials (mainly carbon-based nanomaterials, lipid materials, polymers, etc.) and inorganic nanomaterials (mainly noble metal nanoparticles, magnetic nanoparticles, hollow mesoporous materials, etc.). The challenges and prospects for the future development of targeted nanomaterials in the treatment of leukemia are also briefly reviewed. more...
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- 2024
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5. Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma
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Wen Lei, Ai Zhao, Hui Liu, Chunmei Yang, Cheng Wei, Shanshan Guo, Zhilu Chen, Qunyi Guo, Linjie Li, Mingzhe Zhao, Gongqiang Wu, Guifang Ouyang, Ming Liu, Jinyi Zhang, Jimin Gao, and Wenbin Qian
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Cytology ,QH573-671 - Abstract
Abstract Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106–4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL. more...
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- 2024
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6. Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma
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Jing Yang, Feifan Jin, Huanjuan Li, Yuhuan Shen, Weilin Shi, Lina Wang, Lei Zhong, Gongqiang Wu, Qiaoliang Wu, and Yanchun Li
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Stomach adenocarcinoma ,Mitochondrial complexes ,Tumor microenvironment ,Microsatellite instability ,Prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Stomach adenocarcinoma (STAD) is the third leading cause of cancer-related deaths and the fifth most prevalent malignancy worldwide. Mitochondrial respiratory chain complexes play a crucial role in STAD pathogenesis. However, how mitochondrial respiratory chain complex genes (MRCCGs) affect the prognosis and tumor microenvironment in STAD remains unclear. In this study, we systematically analyzed genetic alterations and copy number variations of different expression densities of MRCCGs, based on 806 samples from two independent STAD cohorts. Then we employed the unsupervised clustering method to classify the samples into three expression patterns based on the prognostic MRCCG expressions, and found that they were involved in different biological pathways and correlated with the clinicopathological characteristics, immune cell infiltration, and prognosis of STAD. Subsequently, we conducted a univariate Cox regression analysis to identify the prognostic value of 1175 subtype-related differentially expressed genes (DEGs) and screened out 555 prognostic-related genes. Principal component analysis was performed and developed the MG score system to quantify MRCCG patterns of STAD. The prognostic significance of MG Score was validated in three cohorts. The low MG score group, characterized by increased microsatellite instability-high (MSI-H), tumor mutation burden (TMB), PD-L1 expression, had a better prognosis. Interestingly, we demonstrated MRCCG patterns score could predict the sensitivity to ferroptosis inducing therapy. Our comprehensive analysis of MRCCGs in STAD demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. Our findings highlight that MRCCGs may provide a new understanding of immunotherapy strategies for gastric cancer and provide a new perspective on the development of personalized immune therapeutic strategies for patients with STAD. more...
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- 2023
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7. Peripheral immune cell profiling of double-hit lymphoma by mass cytometry
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Tao Lei, Gongqiang Wu, Yongjin Xu, Weihao Zhuang, Jialiang Lu, Shuiyun Han, Yuxin Zhuang, Xiaowu Dong, and Haiyan Yang
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Double-hit Lymphoma ,Peripheral blood ,Immune cells ,CyTOF ,CD38 ,Heterogeneity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Double-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements of MYC and BCL2 and/or BCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity. Methods We collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics. Results We found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlighted TP53 as a major factor that contributes to the heterogeneity of the T cells profile. Conclusion Our study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL. more...
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- 2023
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8. P744: A REAL-WORLD STUDY OF MULTIPLE-CYCLE HYPOMETHYLATING AGENTS MONOTHERAPY IN MYELODYSPLASTIC SYNDROMES
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Xiaozhen Liu, Huifang Jiang, Guifang Ouyang, Shujuan Zhou, Jiang Huang, Jin Zhang, Caifang Zhao, Yanping Shao, Gongqiang Wu, Xibin Xiao, Chen Mei, Gaixiang Xu, Liya MA, Xinping Zhou, Yanling Ren, and Hongyan Tong more...
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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9. Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia
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Gongqiang Wu, Shanshan Guo, Qian Luo, Xiaoxia Wang, Wenhai Deng, Guifang Ouyang, Jeffrey J. Pu, Wen Lei, and Wenbin Qian
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CD70 ,CAR-T ,immunotherapy ,leukemia stem cells ,acute myeloid leukemia ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundsChimeric antigen receptor (CAR)-T cell therapy has achieved unprecedented success in treating hematopoietic malignancies. However, this cell therapy is hampered in treating acute myeloid leukemia (AML) due to lack of ideal cell surface targets that only express on AML blasts and leukemia stem cells (LSCs) but not on normal hematopoietic stem cells (HSCs).MethodsWe detected the CD70 expression on the surfaces of AML cell lines, primary AML cells, HSC, and peripheral blood cells and generated a second-generation CD70-specific CAR-T cells using a construct containing a humanized 41D12-based scFv and a 41BB-CD3ζ intracellular signaling domain. Cytotoxicity, cytokine release, and proliferation in antigen stimulation, CD107a assay, and CFSE assays were used to demonstrate the potent anti-leukemia activity in vitro. A Molm-13 xenograft mouse model was established to evaluate the anti-leukemic activity of CD70 CAR-T in vivo. CFU assay was explored to assess the safety of CD70 CAR-T on HSC.ResultsCD70 heterogeneously expressed on AML primary cells, including leukemia blasts, leukemic progenitor, and stem cells, but not expressed on normal HSCs and majority of blood cells. Anti-CD70 CAR-T cells exhibited potent cytotoxicity, cytokines production, and proliferation when incubated with CD70+ AML cell lines. It also displayed robust anti-leukemia activity and prolonged survival in Molm-13 xenograft mouse model. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo.DiscussionOur study reveals that anti-CD70 CAR-T cells are a new potential treatment for AML. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting that future studies aiming to generate innovative combinatorial CAR constructs or to increase CD70 expression density on leukemia cell surface to prolong the life-span of CAR-T cells in the circulation will be needed in order to optimize CAR-T cell responses for AML. more...
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- 2023
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10. Insights on risk score development: Considerations for early-stage hepatocellular carcinoma models.
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Zhanna Zhang and Gongqiang Wu
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- 2025
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11. Sustained Remission of Relapsed or Refractory Mantle Cell Lymphoma After 4-1BB-Based CD19-Directed CAR-T Therapy
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Wen Wen Lei, Wenbin Qian, Aibin Liang, Juying Wei, Hongqiong Xie, Chunmei Yang, and Gongqiang Wu
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0301 basic medicine ,medicine.medical_specialty ,Gastroenterology ,CD19 ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Pharmacology (medical) ,biology ,business.industry ,medicine.disease ,Chimeric antigen receptor ,Lymphoma ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Refractory Mantle Cell Lymphoma ,biology.protein ,Mantle cell lymphoma ,Antibody ,business - Abstract
Relapsed and refractory (R/R) mantle cell lymphoma (MCL) remains an incurable lymphoma with a poor prognosis. Recently, there are a few studies demonstrating the efficacy of anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy in MCL, including ZUMA-2 study in which CD28-based CAR-T cells were used. However, long-term efficacy and safety associated with 4-1BB-based CAR-T therapy in MCL are not defined well. Here, we report three male patients with R/R classical MCL, who received CD19-directed 4-1BB CAR-T therapy and achieved complete remission, showed mild symptoms of cytokine-release syndrome (CRS) and had no neurological toxicity. During a follow-up of 24-35 months, all three patients remained in complete remission. Persistent B-cell depletion was observed in two patients. Recovery of CD19+ polyclonal B cells was detected in one patient at 6 months after CAR-T cell infusion. Recovery of serum immunoglobulin, including IgG, IgA and IgM, was not observed in two patients at the last follow-up. Only one patient developed herpes zoster, and the other two patients had no serious infection. This is the first report about the efficacy, long-term remission and safety of CD19-directed 4-1BB CAR-T therapy in R/R MCL. more...
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- 2020
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12. Genotyping on ctDNA Identifies Shifts in Mutation Spectrum Between Newly Diagnosed and Relapse/Refractory DLBCL
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Yun Liang, Xiaoyan Zhao, Juying Wei, Chunmei Yang, Wenbin Qian, Jing Le, Gongqiang Wu, and Hui Liu
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0301 basic medicine ,Mutation ,business.industry ,breakpoint cluster region ,Gene mutation ,medicine.disease_cause ,medicine.disease ,Malignancy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Biomarker (medicine) ,Pharmacology (medical) ,Liquid biopsy ,business ,Genotyping ,Diffuse large B-cell lymphoma - Abstract
Purpose Diffuse large B cell lymphoma (DLBCL) is an aggressive B-cell malignancy with clinical and molecular heterogeneity whose genetics may have clinical implications for patient stratification and treatment. The circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker harboring tumor-derived genetic alterations that are identical to those of tumor cells, thus showing great promise in individualized medicine, including precise diagnosis, prediction of prognosis, response monitoring, and relapse detection for DLBCL. Patients and methods In this study, we applied NGS analysis to tumor biopsies and ctDNA samples from 16 DLBCL subjects. Then, we compared the genomic alterations from 41 newly diagnosed patients and 56 relapsed/refractory (R/R) patients. Results Our results show that ctDNA can function as a liquid biopsy for tracking recurrently mutated genes in DLBCL (sensitivity: 87.50%). The mutational profiles of newly diagnosed and R/R DLBCL groups largely overlapped, but the frequencies of some gene mutations differ between the two cohorts. The distribution of mutations also revealed different frequencies in the two cohorts due to different signaling pathways. Genes from apoptosis pathway, immune response and BCR pathway suffered more mutations in R/R patients. Conclusion Overall, this study establishes ctDNA as an easily accessible source of tumor DNA for DLBCL genotyping and provides a deeper understanding of the somatic alteration spectrum for both newly diagnosed and R/R DLBCL patients. more...
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- 2020
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