A5004604307- CAR-T cell therapy research
- Biomedical Ethics and Regulation
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Chronic Myeloid Leukemia Treatments
- Metabolism, Diabetes, and Cancer
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Peroxisome Proliferator-Activated Receptors
- T-cell and Retrovirus Studies
- Remote Sensing and Land Use
- Viral Infectious Diseases and Gene Expression in Insects
- Biosensors and Analytical Detection
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Inflammatory mediators and NSAID effects
- Fibroblast Growth Factor Research
- Congenital Diaphragmatic Hernia Studies
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
Memorial Sloan Kettering Cancer Center
2022-2025
Wenzhou Medical University
2023
Newcastle University
2017-2022
Xiamen University
2011-2016
Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that genetic disruption SUV39H1, which encodes histone-3, lysine-9 methyl-transferase, enhances early expansion, long-term persistence, and overall antitumor human CAR in leukemia prostate cancer models. Persisting SUV39H1-edited demonstrate improved expansion tumor rejection upon...
The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with lineage switch from to myeloid leukemia, resulting in poor clinical outcomes caused by resistance chemotherapies and immunotherapies. In this study, the relapses shared oncogene breakpoints their matched lymphoid presentations originated various differentiation stages immature progenitors through committed B-cell precursors. Lineage switching is linked substantial changes...
Chimeric antigen receptor T cells have dramatically improved the treatment of hematologic malignancies. cell (TCR)-based therapies are yet to achieve comparable outcomes. Importantly, chimeric receptors not only target selected antigens but also reprogram functions through co-stimulatory pathways that they engage upon recognition. We show here a fusion comprising CD80 ectodomain and 4-1BB cytoplasmic domain, termed 80BB, acts as both ligand CD28 pathways, thereby increasing antitumor potency...
T-cell Acute Lymphoblastic Leukemia (T-ALL) is frequently characterized by glucocorticoid (GC) resistance, which associated with inferior outcomes, thus highlighting the need for novel therapeutic approaches GC resistant T-ALL. The pTCR/TCR signaling pathways play a critical role in cell fate decisions during physiological thymocyte development, an interplay between TCR and receptor (GR) determining T-lymphocyte selection process. We performed shRNA screen vitro vivo T-ALL lines patient...
Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life‐threatening disease without an effective drug at present. Fibroblast growth factor 21 (FGF21) was reported to be protective against inflammation in metabolic recent studies. However, the role of FGF21 ALI has been rarely investigated. In this study, it found that expression markedly increased tissue under lipopolysaccharide (LPS) stimulation vivo , whereas decreased epithelial cells LPS vitro . Therefore,...
<p>Key Resources Table</p>
<p>Figure S6.Increased proliferation and reduced effector function in 1928z CAR T cells upon SUV39H1 disruption.</p>
<p>Figure S3. CAR T cell inhibitory receptor expression.</p>
<p>Key Resources Table</p>
<p>Figure S7. SUV39H1 disruption, over time, improves expansion and cytolytic capacity of CAR T cells under conditions repeated stimulation.</p>
<p>Figure S8. SUV39H1 disruption enhances CAR T cell persistence.</p>
<p>Figure S9. Enhanced TCF1 and LEF1 expression in SUV39H1-edited CAR T cells under conditions of repeated stimulation.</p>
<p>Figure S6.Increased proliferation and reduced effector function in 1928z CAR T cells upon SUV39H1 disruption.</p>
<div>Abstract<p>Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that genetic disruption <i>SUV39H1</i>, which encodes histone-3, lysine-9 methyl-transferase, enhances early expansion, long-term persistence, and overall antitumor human CAR in leukemia prostate cancer models. Persisting...
<p>Figure S1. Phenotype of T cells (at isolation) and CAR (pre-infusion).</p>
<p>Figure S5. SUV39H1 disruption improves anti-tumor efficacy of multiple CAR designs in a prostate cancer model.</p>
<p>Figure S4. Off-target editing of the SUV39H1 gRNA.</p>
<p>Figure S7. SUV39H1 disruption, over time, improves expansion and cytolytic capacity of CAR T cells under conditions repeated stimulation.</p>
<p>Figure S3. CAR T cell inhibitory receptor expression.</p>