Dieter Schiegg
A5050607505- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- SARS-CoV-2 and COVID-19 Research
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Nanoparticle-Based Drug Delivery
- PARP inhibition in cancer therapy
- Viral Infections and Immunology Research
- Advanced Breast Cancer Therapies
- vaccines and immunoinformatics approaches
- Advanced biosensing and bioanalysis techniques
- Click Chemistry and Applications
Molecular Partners (Switzerland)
2017-2024
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage three units spike protein trimer SARS-CoV-2 and inhibit ACE2 binding high potency, as revealed by cryo-electron microscopy analysis. cooperative together...
Abstract Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well rapid large-scale production capabilities. Highly potent multivalent low picomolar virus neutralization efficacies were generated by molecular linkage three different monovalent molecules. These target various domains spike protein, thereby limiting possible viral escape. Cryo-EM analysis individual...
Abstract The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit not eligible hematopoietic stem cell (HSC) transplantation. disease driven by leukemic cells (LSCs), which are characterized clonal heterogeneity and resistance to conventional therapy. These therefore believed be a major cause progression relapse. We designed MP0533, multispecific CD3-engaging ankyrin repeat protein (DARPin) that can simultaneously bind three antigens on AML...
Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant vaccine induced immunity therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study ensovibep, first trispecific clinical DARPin candidate, that simultaneously engage all three units spike protein trimer potently inhibit ACE2 interaction, as revealed by structural analyses. The...
PD-1/PD-L1 blockade has revolutionized the field of immunooncology. Despite relative success, response rate to anti-PD-1 therapy requires further improvements. Our aim was explore enhancement T-cell function by using novel PD-1-blocking proteins and compare with clinically approved monoclonal antibodies (mAbs). We isolated T-cells from ascites tumor 17 patients advanced epithelial ovarian cancer (EOC) analyzed effects mAbs nivolumab pembrolizumab two engineered ankyrin repeat (DARPin®...
<div>Abstract<p>The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit not eligible hematopoietic stem cell (HSC) transplantation. The disease driven by leukemic cells (LSCs), which are characterized clonal heterogeneity and resistance to conventional therapy. These therefore believed be a major cause progression relapse. We designed MP0533, multispecific CD3-engaging ankyrin repeat protein (DARPin) that can simultaneously bind...
<div>Abstract<p>The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit not eligible hematopoietic stem cell (HSC) transplantation. The disease driven by leukemic cells (LSCs), which are characterized clonal heterogeneity and resistance to conventional therapy. These therefore believed be a major cause progression relapse. We designed MP0533, multispecific CD3-engaging ankyrin repeat protein (DARPin) that can simultaneously bind...
<p>Supplementary Fig. S12.</p>
<p>Supplementary Fig. S1. MP0533 format comparison.</p>
<p>Supplementary Fig. S12.</p>
<p>Supplementary Fig. S16. Binding to HUVEC cells.</p>
<p>Supplementary Fig. S2. MP0533 affinity traces and simultaneous binding to its targets.</p>
<p>Supplementary Fig. S15. TCE-induced CD70 upregulation on activated CD4 and CD8 T cells. Expression of cells in cocultures with MOLM-13 1 nmol/L MP0533 or CD123-CD3 DART.</p>
<p>Supplementary Fig. S2. MP0533 affinity traces and simultaneous binding to its targets.</p>
<p>Supplementary Fig. S3. TAA quantification on healthy blood cells.</p>
<p>Supplementary Fig. S5. TAA expression on AML and healthy donor samples.</p>
<p>Supplementary Fig. S5. TAA expression on AML and healthy donor samples.</p>
<p>Supplementary Fig. S16. Binding to HUVEC cells.</p>
<p>Supplementary Fig. S13. MP0533 safety profile in hPBMC mouse model xenografted intravenously with MOLM-13 cells.</p>
<p>Supplementary Fig. S1. MP0533 format comparison.</p>
<p>Supplementary Fig. S17. TAA expression analysis on AML PDX cells.</p>
<p>Supplementary Fig. S10. Competition/inhibition with soluble ligands/TAAs.</p>
<p>Supplementary Fig. S14. Killing of healthy cells.</p>
<p>Supplementary Fig. S4. MP0533 induces similar low cytokine release with pan T or PBMC as effector cells.</p>
<p>Supplementary Fig. S4. MP0533 induces similar low cytokine release with pan T or PBMC as effector cells.</p>