- CAR-T cell therapy research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Integrated Circuits and Semiconductor Failure Analysis
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Silicon Carbide Semiconductor Technologies
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Advancements in Semiconductor Devices and Circuit Design
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Biomedical Ethics and Regulation
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Biosimilars and Bioanalytical Methods
- Biochemical and Molecular Research
- Single-cell and spatial transcriptomics
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
Second Affiliated Hospital of Zhejiang University
2020-2024
Xuzhou Medical College
2020-2024
National Institutes of Health
2009-2024
Beijing Hospital
2020-2023
Zhejiang University
2022-2023
Nanfang Hospital
2022
Nanjing Drum Tower Hospital
2022
Chinese Academy of Sciences
2014-2022
Nanjing Agricultural University
2022
Shandong Agricultural University
2022
Abstract CD19-specific chimeric antigen receptor (CAR) T-cell therapy is highly effective against relapsed or refractory acute lymphoblastic leukemia (ALL), but hindered by neurotoxicity. In 53 adult patients with ALL, we found a significant association of severe neurotoxicity high pretreatment disease burden, higher peak CAR expansion, and early elevations proinflammatory cytokines in blood. Patients had evidence blood–cerebrospinal fluid (CSF) barrier disruption correlating grade without...
Adoptive cell transfer (ACT) of purified naive, stem memory, and central memory T subsets results in superior persistence antitumor immunity compared with ACT populations containing more-differentiated effector cells. Despite a clear advantage the less-differentiated populations, majority trials utilize unfractionated subsets. Here, we have challenged notion that mere presence cells starting used to generate therapeutic is sufficient convey their desirable attributes. Using both mouse human...
Abstract Background Despite numerous chimeric antigen receptor T‐cell (CAR‐T) trials conducted in China, no CAR‐T has been registered the country. Furthermore, China law and regulations restrict export of patient material for manufacture abroad. Relma‐cel (JWCAR029), an anti‐CD19 product produced with a commercial‐ready process was evaluated first prospective, single‐arm, multicenter, pivotal study therapy under Chinese IND to support NMPA‐accepted BLA submission relapsed/refractory (r/r)...
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 tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T could overcome suppressive milieu, but the clinical safety and efficacy of this therapy remain unclear. Here we report preclinical development capable expressing interleukin (IL)-7 chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement...
Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that costly and poorly accessible to patients. We aimed evaluate the safety antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. report results from first-in-human, open-label, single-dose, phase 1 study CD19-specific CAR (CAR-DNT) cells.
Two novel binuclear complexes [Cu2(L)]·(ClO4)2 (1) and [Zn2(L)]·(ClO4)2 (2) were synthesized crystallographically characterized {L = 14,54-dimethyl-12,52-dihydroxy-1(1,3),5(1,3)-dibenzene-3(1,4),7(1,4)-di-1,4,7-triazacyclononane}. The cation [Cu2(L)]2+ structure of 1 is similar to that [Zn2(L)]2+ 2. central ion bridged by the di-phenoxo L lies in a close perfect square pyramidal geometry. 2 crystallize triclinic space group P. two effectively promote cleavage plasmid DNA presence activating...
Abstract Purpose Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B lymphoma (R/R DLBCL). However, this failed in nearly 25% patients mainly due to loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 anti‐CD20 CAR‐T cells treatment R/R DLBCL evaluated its toxicity. Methods Totally 21 with were enrolled study. conditioned fludarabine cyclophosphamide before the infusion cells....
Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are most commonly used in manufacturing process. However, integration pattern these viral subsequent effect on products is still unclear.We modified sites analysis (VISA) pipeline to evaluate events around whole genome pre-infusion products. We compared differences between lentiviral also explored whether correlated...
We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, aldesleukin) consistently activates tumor-associated macrophages and upregulates IFN-stimulated genes while inducing minimal migration, activation, or proliferation of T cells. These effects are independent tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMC) melanoma metastases.We gene expression changes serially...
In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+ T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) response. Here, further characterized this CD8+BTLA+ TIL subset their CD8+BTLA− counterparts. We that BTLA+ TILs had increased response to IL-2, were less-differentiated effector-memory (TEM) cells, persisted longer vivo after...
Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are primary collagen-producing cells fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, some, such as suberoylanilide hydroxamic acid (SAHA), US FDA approved for cancer treatment. In this study, we investigated SAHA’s effects on expression of III alpha 1 (COL3A1) human IPF fibroblasts murine model We observed...
Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) is a for metastatic melanoma response rates of up to 50%. However, the generation TIL transfer product challenging, requiring pooled allogeneic normal donor peripheral blood mononuclear cells (PBMC) used in vitro as "feeders" support rapid-expansion protocol. Here, we optimized platform propagate clinical scale using K562 genetically modified express costimulatory molecules such CD86, CD137-ligand, and membrane-bound...
Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one which is dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR function. In this study, effects on functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different T cells (CD133-specific HER2-specific CAR) prepared, corresponding target including human glioma line U251 CD133-OE that overexpress CD133 breast cancer...
Abstract Rationale A high risk of post‐operative recurrence contributes to the poor prognosis and low survival rate oesophageal squamous cell carcinoma (ESCC) patients. Increasing experimental evidence suggests that integrin adhesion receptors, in particular αv (ITGAV), are important for cancer survival, proliferation migration. Therefore, targeting ITGAV may be a rational approach preventing ESCC recurrence. Materials methods Protein levels were determined human tumour tissues using...
Tumor cells are characterized by their high rate of glycolysis and clotrimazole has been shown to disrupt the pathway thereby arresting in G1 cell cycle phase. Herein, we present data support our hypothesis that arrests tumor a radiosensitizing, late The effects were studied using glioblastoma line, U-87 MG. Flow cytometry was used analyze redistribution induction apoptosis. Immunoblots probed characterize arrest. Nuclear cytoplasmic fractions collected follow clotrimazole-induced...
Abstract Background Genetically engineered T cells have become an important therapy for B-cell malignancies. Measuring the efficiency of vector integration into cell genome is assessing potency and safety these cancer immunotherapies. Methods A digital droplet polymerase chain reaction (ddPCR) assay was developed evaluated average number lenti- retroviral vectors integrated Chimeric Antigen Receptor (CAR) Cell (TCR)-engineered cells. Results The ddPCR consistently measured concentration...
Background aimsReference genes are an essential part of clinical assays such as droplet digital polymerase chain reaction (ddPCR), which measure the number copies vector integrated into genetically engineered cells and loss plasmids in reprogrammed used cell therapies. Care should be taken to select reference genes, because it has been discovered that there may thousands variations copy from genomic segments among different individuals. In addition, within same person context cancer other...
Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth assayed; cycle analyzed flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK) cyclin D1 promoter activities were...