A5031555353- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Biosimilars and Bioanalytical Methods
- Protein Kinase Regulation and GTPase Signaling
- Neuroblastoma Research and Treatments
- Nitric Oxide and Endothelin Effects
- Metabolism, Diabetes, and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- vaccines and immunoinformatics approaches
- Cardiomyopathy and Myosin Studies
Center for Cancer Research
2023
National Cancer Institute
2018-2019
Harvard University
2009-2012
Brigham and Women's Hospital
2009
T cell receptor (TCR) therapy is a promising cancer treatment modality. However, its successful development for epithelial cancers may depend on the identification of high-avidity TCRs directed against tumor-restricted target antigens. The human papillomavirus (HPV) E7 antigen an attractive therapeutic that constitutively expressed by HPV+ but not healthy tissues. It unknown if genetically engineered TCR cells can mediate regression cancers. We identified HPV-16 E7-specific,...
Chimeric antigen receptor (CAR) and T-cell (TCR) therapies are effective in a subset of patients with solid tumors, but new approaches needed to universally improve patient outcomes. Here, we developed technology leverage the cooperative effects IL15 IL21, two common cytokine-receptor gamma chain family members distinct, pleiotropic on T cells other lymphocytes, enhance efficacy adoptive cells.
T cell receptor (TCR) gene-engineered cells have shown promise in the treatment of melanoma and synovial sarcoma, but their application to epithelial cancers has been limited. The identification novel therapeutic TCRs for targeting these tumors is important development new treatments. Here, we describe preclinical characterization a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by <i>CT83</i>), cancer germline antigen with frequent expression human malignancies...
Hydrogen peroxide and other reactive oxygen species are intimately involved in endothelial cell signaling. In many types, the AMP-activated protein kinase (AMPK) has been implicated control of metabolic responses, but role redox signaling modulation AMPK remains to be completely defined. We used RNA interference pharmacological methods establish that H(2)O(2) is a critical activator cultured bovine aortic cells (BAECs). treatment BAECs rapidly significantly increases phosphorylation AMPK....
Impairment of endothelial barrier function is implicated in many vascular and inflammatory disorders. One prevalent mechanism dysfunction an increase reactive oxygen species under oxidative stress. Previous reports have demonstrated that hydrogen peroxide (H 2 O ), a highly stable modulates physiological signaling pathways, also enhances permeability, but the this effect unknown. Here, we identify actin-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) as key mediator H...
Vasodilator-stimulated phosphoprotein (VASP) is a major substrate for cyclic nucleotide-dependent kinases that has been implicated in cardiac pathology, yet many aspects of VASP's molecular regulation cardiomyocytes are incompletely understood. In these studies, we explored the role VASP, both signaling pathways isolated murine myocytes, as well model hypertrophy VASP(null) mice. We found beta-adrenergic agonist isoproterenol promotes rapid and reversible phosphorylation VASP at Ser157...
e15048 Background: T-cell receptor (TCR) gene-engineered T cell therapy is a promising cancer treatment strategy. Its successful development for epithelial cancers may depend on the identification of high-avidity TCRs directed against tumor-restricted target antigens. The human papillomavirus (HPV) E7 antigen constitutively expressed by HPV+ but not healthy tissues. Here, we report discovery and preclinical testing TCR that targets HPV-16 E7. Methods: Cervix-infiltrating T-cells from women...
<div>AbstractPurpose:<p>Chimeric antigen receptor (CAR) and T-cell (TCR) therapies are effective in a subset of patients with solid tumors, but new approaches needed to universally improve patient outcomes. Here, we developed technology leverage the cooperative effects IL15 IL21, two common cytokine-receptor gamma chain family members distinct, pleiotropic on T cells other lymphocytes, enhance efficacy adoptive cells.</p>Experimental Design:<p>We designed vectors that...
<p>Replicate in vivo adoptive TCR T-cell studies.</p>
<p>In vitro shedding studies.</p>
<p>In vitro shedding studies.</p>
<p>Violin plots showing common marker expression by cluster.</p>
<p>Violin plots showing common marker expression by cluster.</p>
<p>Body weights from mice with orthotopic neuroblastoma that were treated adoptive T-cells.</p>
<p>In vitro shedding studies.</p>
<p>Replicate in vivo adoptive TCR T-cell studies.</p>
<p>Predicted cytokine structure and expression.</p>
<p>Violin plots showing common marker expression by cluster.</p>
<p>Replicate CAR T-cell studies.</p>
<p>Predicted cytokine structure and expression.</p>
<p>Violin plots showing common marker expression by cluster.</p>
<p>Replicate rechallenge experiment in vitro.</p>
<p>Body weights from mice with orthotopic neuroblastoma that were treated adoptive T-cells.</p>
<p>In vitro shedding studies.</p>