Sebastian Grimm
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Transgenic Plants and Applications
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Spectroscopy and Quantum Chemical Studies
- Animal Virus Infections Studies
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Herpesvirus Infections and Treatments
- Lipid Membrane Structure and Behavior
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
Molecular Partners (Switzerland)
2024
Dartmouth College
2012-2015
Interactions of cytochrome c (cyt c) with cardiolipin (CL) partially unfold the protein, activating its peroxidase function, a critical event in execution apoptosis. However, structural features altered protein species heterogeneous ensemble are difficult to probe averaging. Analyses dye-to-heme distance distributions P(r) from time-resolved FRET (TR-FRET) have uncovered two distinct types CL-bound cyt conformations, extended and compact. We combined TR-FRET, fluorescence correlation...
Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated HIV-1-infected individuals with autoimmune disease defective mechanisms may produce BnAbs readily than those without diseases. In this study, we identified...
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...
Major advances in donor identification, antigen probe design, and experimental methods to clone pathogen-specific antibodies have led an exponential growth the number of newly characterized broadly neutralizing (bnAbs) that recognize HIV-1 envelope glycoprotein. Characterization these bnAbs has defined new epitopes novel modes recognition can result potent neutralization HIV-1. However, translation profiles biophysical assays into understanding vivo activity lagged behind, identification...
Design of an envelope-based immunogen capable inducing a broadly neutralizing antibody response is thought to be key the development protective HIV-1 vaccine. However, broad diversity viral variants and limited ability produce native envelope have hampered such design efforts. Here we describe adaptation yeast display system use combinatorial protein engineering approach permit directed evolution HIV variants. Because intrinsic instability complexity this trimeric glycoprotein has greatly...
<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>