A5036334760- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Pancreatic function and diabetes
- Diet and metabolism studies
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Diet, Metabolism, and Disease
University of Pennsylvania
2023-2024
Chimeric antigen receptor (CAR) T cell dysfunction is a major barrier to achieving lasting remission in hematologic cancers, especially chronic lymphocytic leukemia (CLL). We have shown previously that Δ133p53α, an endogenous isoform of the human TP53 gene, decreases expression with age cells, and reconstitution Δ133p53α poorly functional cells can rescue proliferation [A. M. Mondal
Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons mbIL15 to NK expansion lack key attributes resulting cells, including their high-dimensional phenotype, polyfunctionality, breadth and potency cytotoxicity, cellular metabolism, activity in xenograft tumor models. Moreover, despite multiple rounds stimulation, studies...
Abstract Patients with multiple myeloma (MM) treated B-cell maturation antigen (BCMA)-specific chimeric receptor (CAR) T cells usually relapse BCMA+ disease, indicative of CAR T-cell suppression. CD200 is an immune checkpoint that overexpressed on aberrant plasma (aPCs) in MM and independent negative prognostic factor for survival. However, not present cell lines, a potential limitation current preclinical models. We engineered lines to express at levels equivalent those found aPCs show...
Early expansion and long-term persistence predict efficacy of chimeric antigen receptor T cells (CARTs)
<h3>Background</h3> The success of CAR T-cell immunotherapy depends on the differentiation status and metabolic fitness product. In current CART manufacturing protocols, activation leads to irreversible differentiation. Our recent work showed that nonactivated T-cells can be generated within 24 hours, eliminating need for or <i>ex vivo</i> expansion. We assert this process retains maximal Interleukin 18 (IL-18) is a proinflammatory cytokine regulates adoptively transferred T-cells, IL-18...
Activated T cells undergo a metabolic shift to aerobic glycolysis support the energetic demands of proliferation, differentiation, and cytolytic function. Transmembrane glucose flux is facilitated by transporters (GLUT) that play vital role in cell reprogramming anti-tumour GLUT isoforms are regulated at level expression subcellular distribution. GLUTs also display preferential selectivity for carbohydrate macronutrients including glucose, galactose, fructose. GLUT5, which selectively...
<p>Figure S4. Expressions of the immune checkpoints on freshly isolated-NK cells and expanded-NK cells</p>
<p>Figure S7. Pearson correlation, heatmap, and GSEA analysis of Bulk RNA-Seq data</p>
<div>Abstract<p>Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons mbIL15 to NK expansion lack key attributes resulting cells, including their high-dimensional phenotype, polyfunctionality, breadth and potency cytotoxicity, cellular metabolism, activity in xenograft tumor models. Moreover, despite multiple rounds...
<p>Figure S6. Isoplexis-tSNE plots and polyfunctionality heatmap of single-cell secretome</p>
<p>Figure S6. Isoplexis-tSNE plots and polyfunctionality heatmap of single-cell secretome</p>
<div>Abstract<p>Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons mbIL15 to NK expansion lack key attributes resulting cells, including their high-dimensional phenotype, polyfunctionality, breadth and potency cytotoxicity, cellular metabolism, activity in xenograft tumor models. Moreover, despite multiple rounds...
<p>Figure S2. Representative flow plots of SSA against FSA and the expression CD56 CD3 NK 2 cells as well gating strategy for counting cells</p>
<p>Figure S7. Pearson correlation, heatmap, and GSEA analysis of Bulk RNA-Seq data</p>
<p>Figure S5. Statistical analysis of the cytotoxicity expanded-NK cells against different tumor targets and their degranulation.</p>
<p>Figure S3. Expressions of activating receptors and cell death ligands on freshly isolated-NK cells 2 expanded-NK cells.</p>
<p>Figure S1. mbIL-21 structure and the effect of K562 expressing CD40 on NK cell expansion</p>
<p>Figure S1. mbIL-21 structure and the effect of K562 expressing CD40 on NK cell expansion</p>
<p>Figure S2. Representative flow plots of SSA against FSA and the expression CD56 CD3 NK 2 cells as well gating strategy for counting cells</p>