Stefanie Briner
A5070858940- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CAR-T cell therapy research
- Viral Infections and Immunology Research
- Blood disorders and treatments
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Advanced Biosensing Techniques and Applications
- Blood groups and transfusion
- Cytomegalovirus and herpesvirus research
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Electron Microscopy Techniques and Applications
Roche (Switzerland)
2022-2024
Effective T-cell responses not only require the engagement of receptors (TCRs; "signal 1"), but also availability costimulatory signals ("signal 2"). bispecific antibodies (TCBs) deliver a robust signal 1 by engaging TCR signaling component CD3ε, while simultaneously binding to tumor antigens. The CD20-TCB glofitamab redirects T cells CD20-expressing malignant B cells. Although exhibits strong single-agent efficacy, adding may enhance depth and durability T-cell-mediated cell killing. We...
Target-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine syndrome (CRS), highlighting need to understand prevent this complex clinical syndrome.We explored cellular molecular players involved TCB-mediated by single-cell RNA-sequencing whole blood treated with CD20-TCB together bulk endothelial cells exposed TCB-induced release. We used vitro assay an vivo DLBCL model immunocompetent humanized mice assess effects dexamethasone,...
Abstract T-cell bispecific antibodies (TCB) are engineered molecules that bind both the receptor and tumor-specific antigens. Epidermal growth factor variant III (EGFRvIII) mutation is a common event in glioblastoma (GBM) characterized by deletion of exons 2–7, resulting constitutively active promotes cell proliferation, angiogenesis, invasion. EGFRvIII expressed on surface tumor cells not normal tissues, making an ideal neoantigen target for TCBs. We designed developed novel 2+1...
<p>Supplementary Figure S9. Single cell RNA-sequencing of whole blood treated with 0.2 μg/mL CD20-TCB was performed using the BD Rhapsody platform</p>
<p>Supplementary Figure S8. Single cell RNA-sequencing of whole blood treated with 0.2 μg/mL CD20-TCB was performed using the BD Rhapsody platform.</p>
<p>Supplementary Figure S7. Overview of average expression and fraction positives per cell type, timepoint treatment condition for cytokines that are differentially expressed in neutrophils, monocytes, pDC, cDC, B cells, CD4+ T CD8+ MAIT cells and/or NK vs. control any timepoint. The untreated corresponds to the pooled baseline samples incubation samples. Mean n= 4 donors (baseline, 20 hrs) n=2 (2 hrs, hrs 6 hrs).</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S12. Individual tumor growth curves for each treatment group. OCI-Ly18 (DLBCL)-bearing humanized NSG mice were pre-treated with 30 mg/kg Gazyva (Gpt, grey arrow) and treated weekly escalating doses of CD20-TCB (0.5 mg/kg, 1 2 red arrows). Adalimumab (25 orange arrow, TNF-α blockade) tocilizumab (10 green IL-6R given day hour before the first infusion. Dexamethasone (1 blue was prior therapy. Anakinra purple IL-1R NLRP3 inhibitor (20 light administered before, 4...
<p>Supplementary Figure S1. Levels of cytokines were measured by Luminex in serum from whole blood assay with CD20-TCB. 1 donor.</p>
<p>Supplementary Figure S13. A. 3D in vitro experimental setup. Human PBMCs and SU-DHL-8 tumor cells were co-cultured a ratio of 5:1 treated with 0.01 nM CD20-TCB the presence or absence 5 μg/mL adalimumab for 24 hrs. Supernatant from co-cultures was transferred to bottom channel Mimetas OrganoPlate®. derived same donor as co-cultures, are fluorescently labeled seeded upper OrganoPlate®, where endothelial tubules have been previously formed. OrganoPlate® then imaged Operetta System...
<p>Supplementary Figure S3. Identification of an interacting B and T cells cluster by scRNA sequencing human whole blood treated with 0.2 μg/mL CD20-TCB using the BD Rhapsody platform.</p>
<p>Supplementary Figure S2. Proportions of T cells, monocytes and neutrophils in human whole blood after treatment with 0.2 μg/mL CD20-TCB</p>
<p>Supplementary Figure S10. Single cell RNA-sequencing of whole blood treated with 0.2 μg/mL CD20-TCB was performed using the BD Rhapsody platform</p>
<p>Supplementary Figure S11. Single cell RNA-sequencing of whole blood treated with 0.2 μg/mL CD20-TCB was performed using the BD Rhapsody platform. A. UMAP plots neutrophils colored by treatment. B. showing IL-1β (IL1B), IL-1Ra (IL1RN), IL-6 (IL6), IP-10 (CXCL10), IL-8 (CXCL8), TNF-α (TNF), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4) gene expression within neutrophil clusters identified above. C. Violin kinetics distribution in neutrophils. The cytokine and receptor genes are listed on...
<p>Supplementary Figure S5. Overview of GO Biological process pathways found enriched in A. CD4+ T cells (6 hrs), B. CD8+ C. monocytes hrs) and D. neutrophils (4 after treatment with 0.2 μg/mL CD20-TCB.</p>
<p>Supplementary Figure S4. Multidimensional scaling plot of gene expression distances between pseudobulks</p>
<p>Supplementary Figure S6. A. Bulk-rna-sequencing of neutrophils purified from whole blood 4 hrs and 20 following treatment with 0.2 μg/mL CD20-TCB or DP47-TCB for N=4 donors. B. Heat map showing the enriched hallmark pathways in neutrophils, DP47-TCB. C. expression TNF-α (TNF), IL-1β (IL1B), IL-6 (IL6), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4) IP-10 (CXCL10) genes (untargeted TCB). Volcano plots depicting cytokine D. E. after CD20-TCB. Each dot represents one gene. The x axis shows...
<p>Supplementary Methods</p>
<p>Supplementary Figure S7. Overview of average expression and fraction positives per cell type, timepoint treatment condition for cytokines that are differentially expressed in neutrophils, monocytes, pDC, cDC, B cells, CD4+ T CD8+ MAIT cells and/or NK vs. control any timepoint. The untreated corresponds to the pooled baseline samples incubation samples. Mean n= 4 donors (baseline, 20 hrs) n=2 (2 hrs, hrs 6 hrs).</p>