A5032074452- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Nanowire Synthesis and Applications
- Biosimilars and Bioanalytical Methods
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Advancements in Semiconductor Devices and Circuit Design
- Single-cell and spatial transcriptomics
- Chemokine receptors and signaling
- Cytokine Signaling Pathways and Interactions
- Lymphadenopathy Diagnosis and Analysis
- Atherosclerosis and Cardiovascular Diseases
- Silicon Carbide Semiconductor Technologies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- bioluminescence and chemiluminescence research
- Diet and metabolism studies
- CNS Lymphoma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Integrated Circuits and Semiconductor Failure Analysis
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Glioma Diagnosis and Treatment
McMaster University
2016-2023
McMaster University Medical Centre
2021
Princess Margaret Cancer Centre
2018-2019
University of Toronto
2015-2019
Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here authors show that cell coupler (TAC), a receptor co-opts endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared past-generation CARs. TAC-engineered induce robust antigen-specific production cytotoxicity in vitro, strong activity variety of...
Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce cancer but mechanisms mediating this effect remain unclear. In mice humans, a high-fat diet (HFD), metformin are known to alter gut microbiome whether is important for influencing tumor growth not known. Mice with syngeneic MC38 colon adenocarcinomas were treated or feces obtained from control mice. We find that compared chow-fed controls, increased when fed HFD acceleration can be partially...
FCRL4 is an immunoregulatory receptor expressed by a subpopulation of memory B cells. These tissue-based cells express increased levels the src-family kinases HCK and FGR. In this study, we investigate roles these in FCRL4-mediated immunoregulation context previously unrecognized palmitoylation receptor. We observed enhanced phosphorylation on tyrosine residues presence p59 or This was markedly reduced assays using palmitoylation-defective mutant FCRL4. reporter gene studies, observe that...
The adoptive transfer of ex vivo-expanded T cells is a promising approach to treat several malignancies. Several lines evidence support that the infusion with early memory features, capable expanding and persisting after transfer, are associated better outcomes. We report herein exposure exogenous TGFβ during human T-cell stimulation vivo leads accumulation early/central (Tcm) cells. Exposure suppressed expression BLIMP-1, key orchestrator effector differentiation, led upregulation...
PURPOSE: Lymphomas often present a diagnostic challenge, and for some delay in diagnosis can negatively influence outcomes of therapy. We established nurse practitioner–led lymphoma rapid clinic (LRDC) with the goal reducing wait times to definitive diagnosis. examined initial 30-month experience LRDC, results were compared time periods before implementation determine program impact. METHODS: All patients referred LRDC suspicion from June 1, 2015 Nov 30, 2017 evaluated. Time consultation was...
Tumor-targeted chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR-T cells) have demonstrated striking clinical success, but their use has been associated with a constellation of toxicities. A better understanding the pathogenesis these toxicities is required to improve safety profile CAR-T cells. Herein, we describe xenograft model off-tumor cell-associated toxicity. Human cells targeted against HER2 using small-protein binding domain induced acute, dose-dependent in mice. The...
Background aimsT cells engineered with synthetic receptors have delivered powerful therapeutic results for patients relapsed/refractory hematologic malignancies. The authors recently described the T-cell antigen coupler (TAC) receptor, which co-opts endogenous receptor (TCR) and activates T in an HLA-independent manner. Here describe evolution of a next-generation TAC focus on developing TAC-engineered cell multiple myeloma.MethodsTo optimize scaffold, employed bona fide antigen-binding...
Abstract Glioblastoma (GBM), an aggressive primary brain tumor in adults, is feared for its near uniformly fatal prognosis and characterized by a diverse cellular phenotype genetic heterogeneity. Despite the use of multi-modal treatment including surgical resection, radiotherapy chemotherapy, outcome patients with GBM has failed to improve significantly. We developed patient-derived initiating cell (BTIC) early passage lines that describe extent intertumoral heterogeneity, presenting...
Abstract Glioblastoma (GBM), an aggressive primary brain tumor in adults, is feared for its near uniformly fatal prognosis and characterized by a diverse cellular phenotype genetic heterogeneity. Despite the use of multi-modal treatment including surgical resection, radiotherapy chemotherapy, outcome patients with GBM has failed to improve significantly. We developed patient-derived initiating cell (BTIC) early passage lines that describe extent intertumoral heterogeneity, presenting...
<div>Abstract<p>The adoptive transfer of <i>ex vivo</i>–expanded T cells is a promising approach to treat several malignancies. Several lines evidence support that the infusion with early memory features, capable expanding and persisting after transfer, are associated better outcomes. We report herein exposure exogenous TGFβ during human T-cell stimulation vivo</i> leads accumulation early/central (Tcm) cells. Exposure suppressed expression BLIMP-1, key...
<div>Abstract<p>The adoptive transfer of <i>ex vivo</i>–expanded T cells is a promising approach to treat several malignancies. Several lines evidence support that the infusion with early memory features, capable expanding and persisting after transfer, are associated better outcomes. We report herein exposure exogenous TGFβ during human T-cell stimulation vivo</i> leads accumulation early/central (Tcm) cells. Exposure suppressed expression BLIMP-1, key...
<p>TGF-b and CAR transduction</p>
<p>Additional Tcm markers</p>
<p>Figure S3. Ex vivo stimulated Tem do not revert to Tcm</p>
<p>TGF-b and other cytokines</p>
<p>SMAD3 phosphorylation</p>
<p>EBNA1-specific T-cell lines</p>
<p>In vivo bioluminescence, dorsal views</p>
<p>SMAD3 phosphorylation</p>
<p>TGF-b and other cytokines</p>
<p>EBNA1-specific T-cell lines</p>