A5085608791- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Hemoglobin structure and function
- Traumatic Brain Injury and Neurovascular Disturbances
- Blood properties and coagulation
- Nitric Oxide and Endothelin Effects
- Nanoparticle-Based Drug Delivery
- Radiopharmaceutical Chemistry and Applications
- Blood groups and transfusion
- Sepsis Diagnosis and Treatment
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Immune cells in cancer
- Orthopaedic implants and arthroplasty
- Heparin-Induced Thrombocytopenia and Thrombosis
- Viral Infections and Vectors
- Autoimmune and Inflammatory Disorders Research
- Blood Coagulation and Thrombosis Mechanisms
- Immunodeficiency and Autoimmune Disorders
Xencor (United States)
2020-2024
Columbia University Irving Medical Center
2019-2024
Lehigh University
2016-2019
New York University
2018
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2018
Yonsei University
2017
New York Medical College
2017
Renal Research Institute
2017
Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a sensor and receptor. Recently, relatively unstable mechanosensitive domain in the GPIbα subunit of GPIb-IX was identified. Here we show that binding its ligand, von Willebrand factor, under physiological induces unfolding this mechanosensory (MSD) on platelet surface. The unfolded MSD, particularly juxtamembrane 'Trigger' sequence...
Endothelial glycocalyx (EG) is disintegrated during sepsis. We have previously shown that this occurs very early in the course of sepsis and its prevention improves survival mice with Here, we sought to investigate possibility pharmacologically accelerating restoration EG used a soilage injection model induce polymicrobial C57/BL6 measured total body EG. En face aortic preparations were for staining markers atomic force microscopy was measure vitro. In vitro studies conducted cultured...
The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the vascular endothelium, serving critical functions in mechanotransduction of blood flow-induced forces. One most important protective ESG to mediate production nitric oxide (NO) response flow. However, detailed mechanism underlying ESG's NO has not been completely identified. Herein, using cultured rat brain microvascular cells (bEnd.3) as model system, we have implemented combined atomic force and fluorescence...
Abstract Background PD-1 is an immune checkpoint on T cells, and interventions to block this receptor result in cell activation enhanced response tumors pathogens. Reciprocally, despite a decade of research, approaches treat autoimmunity with agonists have only had limited successful. To resolve this, new methods must be developed augment function beyond engaging the receptor. Methods We conducted flow cytometry analysis cells isolated from peripheral blood synovial fluid patients rheumatoid...
<p>XmAb808 enhances T-cell recall responses to endogenous pMHC ligands. <b>A</b> (top graph), Levels of HLA-A2 on A431-β2M-null cells expressing a fusion protein β2M and HLA-A*0201 fused CMV pp65 NLV peptide (A431-NLV, dashed black) or melanoma G209 (A431-G209, solid gray) were compared with the signal from unstained (solid black). (two bottom graphs), PBMCs two unique CMV–seropositive donors stained HLA-A*0201-CMV-pp65 (NLV) tetramers; percentage tetramer+...
<p>XmAb808 enhances the activity of an EpCAM×CD3 TCE <i>in vitro</i>. <b>A</b> and <b>B,</b> 22Rv1-NLR cells were cocultured with T at E:T ratio 10:1 treated a dose titration (closed symbols) or without (open 1 μg/mL XmAb808. <b>A,</b> After 24 hours, IL2 IFNγ secretion was measured, CD25<sup>+</sup> Bcl-xL<sup>+</sup> counted. cell counts are presented as percentage total CD4<sup>+</sup>...
<p>An XmAb808 analogue enhances antitumor activity of an EpCAM×CD3 TCE in human PBMC-engrafted mice. NSG-MHC I/II DKO mice were intradermally inoculated with HPAF-II cells. After 2 weeks, palpable tumors formed, and then engrafted PBMCs together 5 mg/kg alone or combination 1 B7-H3×Null XmAb808<sup>s</sup> weekly. <b>A,</b> Tumor volumes are shown over time as mean ± SEM <i>n</i> = 8–10 mice/group. <b>B,</b> individual at the end study....
<p>XmAb808 binds avidly to B7-H3 on target cells costimulate T cells. <b>A,</b> Binding of XmAb808 or its analogue containing a single B7-H3–binding domain (mono–B7-H3×CD28) with varying densities (left axis) and binding human (right are plotted as mean fluorescence intensity (MFI). HEK293 express approximately 200,000 antigens; A431, 196,000; 22Rv1, 86,000; LOX-IMVI do not B7-H3. Because mono–B7-H3×CD28 has lower molecular weight than (145 vs. 192 kDa), the concentrations...
<p>XmAb808 combines with an anti–PD-1 antibody to suppress tumor growth in human PBMC-engrafted mice. NSG-MHC I/II DKO mice were intradermally inoculated MDA-MB-231-pp65 cells. After 18 days, palpable tumors formed, and engrafted PBMCs together 3 mg/kg of XmAb808 and/or weekly. <b>A,</b> Tumor volumes are shown over time as mean ± SEM 10 mice/group. <b>B,</b> individual at the end study. Each horizontal line represents values. <b>C</b>...
<p>Supplementary Figure S1: XmAb808 Combines With TCEs to Promote IL2 secretion in Naive, Central Memory, Effector and TEMRA T Cells.</p>
<p>Supplementary Figure 2. XmAb808 Combines With a B7-H3×CD3 TCE to Stimulate IL2 and IFNγ Release From Chronically Stimulated, Exhausted T Cells.</p>
<div>Abstract<p>T-cell activation is a multistep process requiring T-cell receptor engagement by peptide–MHC complexes (Signal 1) coupled with CD28-mediated costimulation 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without may be ineffective or even induce anergy. We designed the bispecific antibody XmAb808 to co-engage tumor-associated antigen B7-H3 promote within tumor microenvironment. was measured its...
<p>CD28 costimulation drives activation and survival of T cells, leading to IL2-dependent killing cancer cells. Target cells were cocultured with human (E:T = 1:1) treated XmAb808. <b>A,</b> After 24 hours, IL2 (closed symbols) IFNγ (open measured in culture supernatants. <b>B,</b> The percentages CD4<sup>+</sup> or CD8<sup>+</sup> that CD25<sup>+</sup> Bcl-xL<sup>+</sup> from cocultures 22Rv1-αCD3 following hours...
Abstract Since the most recent outbreak, Ebola virus (EBOV) epidemic remains one of world’s public health and safety concerns. EBOV is a negative-sense RNA that can infect humans non-human primates, causes hemorrhagic fever. It has been proposed T-cell immunoglobulin mucin domain (TIM) family proteins act as cell surface receptors for EBOV, interaction between TIM phosphatidylserine (PS) on mediates EBOV–host attachment. Despite these initial findings, biophysical properties TIM-EBOV...
Abstract T-cell activation is a multistep process requiring receptor engagement by peptide-major histocompatibility complexes (Signal 1) coupled with CD28-mediated costimulation 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without may be ineffective or even induce anergy. We designed the bispecific antibody XmAb808 to co-engage tumor-associated antigen B7-H3 promote within tumor microenvironment. was measured its ability...
The signaling lymphocytic activation molecule (SLAM) family is comprised of nine distinct receptors that are expressed exclusively on hematopoietic cells. Most these transmembrane homotypic by nature and downstream occurs when cells express the same SLAM receptor interact. Previous studies have determined anti-SLAMF6 antibodies can a therapeutic effect in autoimmunity cancer. However, little known about role SLAMF6 adaptive immune responses order to utilize interventional approaches, better...
Signaling lymphocyte activation molecule family member 6 (SLAMF6) is a T cell co-receptor. Previously, we showed that SLAMF6 clustering was required for activation. To better understand the relationship between location and function to evaluate role of as therapeutic target, investigated how its compartmentalization on surface affects functions. We used biochemical co-culture assays show activity enhanced when colocalizes with CD3 complex. Mechanistically, co-immunoprecipitation analysis...
Abstract Programmed cell death 1 (PD-1) is a major coinhibitory receptor and member of the immunological synapse (IS). To uncover proteins that regulate PD-1 recruitment to IS, we searched for cytoskeleton-related also interact with using affinity purification mass spectrometry. Among these proteins, EF hand domain family D2 (EFHD2), calcium binding adaptor protein, was functionally mechanistically analyzed its contribution signaling. EFHD2 required inhibit cytokine secretion, proliferation,...
Abstract PD-1 drives its fame for serving as a pivotal immune checkpoint receptor on T cells. Within the realm of cancer immunotherapy, blocking this triggers cell activation, leading to response against tumors. Conversely, in autoimmunity, agonist is prime candidate effectively suppressing T-cell-driven auto-reactivity and self-tissue damage. Despite decade exploration unlike efficacy agonists treating autoimmunity remains challenge. To overcome hurdle, innovative methods must be devised...