A5100380777- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Biosimilars and Bioanalytical Methods
- Cancer Research and Treatments
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Advancements in Semiconductor Devices and Circuit Design
- Proteoglycans and glycosaminoglycans research
- Wnt/β-catenin signaling in development and cancer
- Peptidase Inhibition and Analysis
- Neuroblastoma Research and Treatments
- Cancer therapeutics and mechanisms
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Silicon Carbide Semiconductor Technologies
- Synthesis and Biological Evaluation
- vaccines and immunoinformatics approaches
- Sarcoma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
Sichuan University
2016-2025
Zhejiang Provincial People's Hospital
2025
Center for Cancer Research
2019-2024
National Cancer Institute
2019-2024
North China Electric Power University
2024
Shanghai Jiao Tong University
2016-2023
National Institutes of Health
2018-2023
State Key Laboratory of Biotherapy
2016-2023
Ruijin Hospital
2022-2023
Shanghai Institute of Hematology
2016-2023
Wnt signaling is one of the key regulators hepatocellular carcinoma (HCC) tumor progression. In addition to classical receptor frizzled (FZD), various coreceptors including heparan sulfate proteoglycans (HSPGs) are involved in activation. Glypican‐3 (GPC3) an HSPG that overexpressed HCC and functions as a coreceptor modulates cell proliferation. These features make GPC3 attractive target for liver cancer therapy. However, precise interaction how GPC3, Wnt, FZD cooperate with each other...
Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in variety of tumors and recognized biomarker circulating tumor stem cells, representing an attractive target adoptive T-cell immunotherapy. This study generated third-generation CAR-T with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The demonstrated that can elicit lytic cytotoxicity...
Abstract Heterogeneous antigen expression is a key barrier influencing the activity of chimeric receptor (CAR) T cells in solid tumors. Here, we develop CAR targeting glypican-1 (GPC1), an oncofetal expressed pancreatic cancer. We report generation dromedary camel V H nanobody (D4)-based GPC1 and optimization hinge (H) transmembrane domain (TM) to improve activity. find that structurally rigid IgG4H CD28TM brings two D4 fragments proximity, driving dimerization leading enhanced T-cell...
Abstract Rational design of chimeric antigen receptor T (CAR-T) cells based on the recognition antigenic epitopes capable evoking most potent CAR activation is an important objective in optimizing immune therapy. In solid tumors, B7-H3 transmembrane protein emerging target that harbours two distinct epitope motifs, IgC and IgV, its ectodomain. Here, we generate dromedary camel nanobodies targeting demonstrate CAR-T cells, recognizing but not IgV domain, had antitumour activity against large...
R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 3 potentiate WNT/β-catenin in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 6 (Lebensohn Rohatgi, 2018). now show heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis engineering. Mutations residues predicted to contact HSPGs impair its capacity. Conversely,...
Abstract Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK are deficient in ligands that target specific tumors, resulting limited antitumor efficacy. Here, glycoengineering approach imitate the chimeric antigen receptor strategy and decorate with nanobodies promote NK‐based solid tumors proposed. Nanobody 7D12, which specifically recognizes human epidermal growth factor (EGFR) overexpressed many coupled chemically synthesized...
Chimeric antigen receptor (CAR)-T cell therapy shows excellent potency against hematological malignancies, but it remains challenging to treat solid tumors, mainly because of a lack appropriate antigenic targets and an immunosuppressive tumor microenvironment (TME). The checkpoint molecule programmed death-ligand 1 (PD-L1) is widely overexpressed in multiple types, the (PD-1)/PD-L1 interaction crucial mediator immunosuppression TME. Here we constructed semi-synthetic shark VNAR phage library...
Significance Due to their small size, nanobodies can recognize protein cavities that are not accessible conventional antibodies. In this report, we built dromedary camel ( Camelus dromedarius ) V H phage libraries for the isolation of high-affinity broadly neutralize SARS-CoV-2 variants. Cryo-EM complex structures reveal one nanobody (8A2) binds S1 subunit viral spike protein, and other (7A3) targets a deeply buried region uniquely extends S2 beyond subunit. These protect mice from lethal...
Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination serous cavities. However, effusions constitute an immune-suppressive environment potentially induces cell dysfunction. Here, we demonstrated anti-tumor cytotoxicity conventional...
Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune and reshape tumor microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of myeloid-derived suppressor cells (MDSCs) decreased T microenvironment (TME) immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed tumors...
Accurate and effective tumor diagnosis, detection, treatment are key for improving the survival rates of patients. Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, hostile microenvironment solid tumors severely prevents CAR-T cells from migrating infiltrating killing malignant cells. Tumor modulation strategies have attracted much attention field cancer immunotherapy. Multifunctional nanoplatforms that...
The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity a target antigen, these models are problematic imitate CAR-T-induced adverse effects in clinic. Epithelial cell adhesion molecule (EpCAM) tumor-associated antigen overtly presented on surface various carcinomas, making it an attractive for therapy. Here, we developed anti-mouse EpCAM CAR evaluate its safety...
Abstract SARS‐CoV‐2 is the etiological agent of COVID‐19 pandemic. Antibody‐based therapeutics targeting spike protein, specifically S1 subunit or receptor binding domain (RBD) SARS‐CoV‐2, have gained attention due to their clinical efficacy in treating patients diagnosed with COVID‐19. An alternative conventional antibody use shark new antigen variable (V NAR ) antibodies. V s are small (<15 kDa) and can reach deep into pockets grooves target antigen. Here, we isolated 53 that bind S2 by...
Objective With the increasing use of fluoroquinolones (FQs) for anti-infective therapy, adverse events (AEs) caused by their collateral effects pose a key challenge in clinical application. Hypoglycemia AEs are type AE linked to FQs and commonly observed real-world settings. Our objective was provide comprehensive analysis summary hypoglycemia associated with FQs, specifically focusing on moxifloxacin (MOX), ciprofloxacin (CPR), levofloxacin (LEV). Methods Disproportionality used assess...