A5039861703- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Lymphoma Diagnosis and Treatment
- Viral Infections and Immunology Research
- Phagocytosis and Immune Regulation
- Blood disorders and treatments
- Adenosine and Purinergic Signaling
- Advanced Biosensing Techniques and Applications
- Blood groups and transfusion
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Biosimilars and Bioanalytical Methods
- Pancreatic function and diabetes
- Erythrocyte Function and Pathophysiology
- Nanoplatforms for cancer theranostics
- Cytomegalovirus and herpesvirus research
- Nanoparticle-Based Drug Delivery
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Click Chemistry and Applications
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
Inhibrx (United States)
2025
Silvus Technologies (United States)
2017-2020
California Institute for Regenerative Medicine
2015-2016
Stanford University
2015-2016
Cancer Institute (WIA)
2015
Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage eliminate malignant B being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety tolerability efficacy of mosunetuzumab in patients with R/R B-NHL established recommended phase II dose. Data from dose escalation are presented. Single-agent was administered intravenously 3-week...
Adenosine signaling through A2A receptors (A2AR) expressed on immune cells suppresses antitumor immunity. CPI-444 is a potent, selective, oral A2AR antagonist. Blockade of with restored T-cell signaling, IL2, and IFNγ production that were suppressed by adenosine analogues in vitro treatment led to dose-dependent inhibition tumor growth multiple syngeneic mouse models. Concentrations extracellular the microenvironment, measured using microdialysis, approximately 100-150 nmol/L higher than...
Agents that block the anti-phagocytic signal CD47 can synergize with pro-phagocytic anti-tumor antigen antibodies to potently eliminate tumors. While is overexpressed on cancer cells, its expression in many normal tissues may create an 'antigen sink' could minimize therapeutic efficacy of blocking agents. Here, we report development bispecific (BsAbs) co-target and CD20, a target for non-Hodgkin lymphoma (NHL), have reduced affinity relative parental antibody, but retain strong binding CD20....
Abstract CD20 is an established therapeutic target in B-cell malignancies. The × CD3 bispecific antibody mosunetuzumab has significant efficacy non-Hodgkin lymphomas (NHLs). Because antigen loss a recognized mechanism of resistance, we evaluated expression relative to clinical response patients with relapsed and/or refractory NHL the phase 1/2 GO29781 trial investigating monotherapy. was studied using immunohistochemistry (IHC), RNA sequencing, and whole-exome sequencing performed centrally...
Abstract Glofitamab, a novel CD20xCD3, T-cell–engaging bispecific antibody, exhibited single-agent activity in Study NP30179, first-in-human, phase 1 trial relapsed/refractory B-cell non-Hodgkin lymphoma. Preclinical studies showed that glofitamab leads to T-cell activation, proliferation, and tumor cell killing upon binding CD20 on malignant cells. Here, we provide evidence of glofitamab’s clinical activity, including pharmacodynamic profile, mode action, factors associated with response,...
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,...
CD47 is highly expressed on a variety of tumor cells. The interaction with signal regulatory protein alpha (SIRPα), phagocytic cells, transmits "don't eat me" that negatively regulates phagocytosis. CD47-SIRPα antagonists enable phagocytosis by disrupting the inhibitory and can synergize Fc-mediated pro-phagocytic signals for potent elimination A potential limitation therapeutic expression normal cells may create sites toxicity or an "antigen sink." To overcome these limitations address...
2505 Background: CPI-006 inhibits CD73, a nucelotidase that converts AMP to adenosine and functions as lymphocyte adhesion molecule. is humanized IgG1 FcγR binding-deficient antibody binds CD73+ T B lymphocytes leading activation of cells expression CD69. This study investigates the immunobiology, safety, efficacy monotherapy in combination with CPI-444, an A2A receptor (A2AR) antagonist (NCT03454451). Methods: Patients relapsed solid tumors were treated 3 + escalation 1, 3, 6 or 12 mg/kg...
7526 Background: Mosunetuzumab (M) is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage eliminate malignant B being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL). an optimal target, with uniform expression across B-NHL histologies minimal receptor turnover. We characterized loss as potential mechanism of resistance M in patients (pts) on Phase I/II trial (NCT02500407) receiving monotherapy the treatment (tx) R/R B-NHL. Methods:...
129 Background: DR5, a proapoptotic receptor, is selectively expressed on tumor vs normal cells, making it an attractive target. DR5 binds to its ligand, TRAIL, resulting in multimerization and apoptosis; greater clustering enhances downstream effects. Ozekibart next-generation, recombinant, humanized, tetravalent agonist that based single-domain antibody platform precisely engineered balance agonism safety. previously demonstrated acceptable safety profile clinical benefit chondrosarcoma...
ABSTRACT COVID-19 is a global pandemic that has resulted in over 800,000 deaths. Robust humoral anti-viral immune responses have the potential to generate diverse set of neutralizing antibodies eliminate viruses and protect against re-infection, transmission, evolution mutations escape targeted therapeutics. CD73 present on majority human B cells subset T where it plays role lymphocyte activation migration. also functions as an ectoenzyme converts AMP into adenosine, which can be...
Abstract Adenosine is present at high concentrations in the tumor microenvironment and immunosuppressive acting on multiple cell types, including suppression of effector T cells. CD73, an ectonucleotidase that converts AMP to adenosine, expressed a subset B cells major source extracellular adenosine. Elevated CD73 expression has been observed types prognostic triple negative breast cancer supporting role for progression1. Inhibiting catalytic activity attractive therapeutic strategy reduce...
Abstract Elevated levels of extracellular adenosine within the tumor microenvironment create an immunosuppressive niche that promotes growth and metastasis. Adenosine signaling via A2A receptor (A2AR) on immune cells suppresses anti-tumor immunity limits efficacy immunotherapies such as anti-PD-L1 or anti-PD-1 monoclonal antibodies (mAbs). CPI-444 is oral A2AR antagonist has been evaluated previously in phase 1 clinical trials for non-oncology indications. demonstrates binding to with a Ki...
Introduction: Glofitamab (RG6026), a T-cell-engaging, bispecific, full-length antibody, allows bivalent binding to CD20 (B-cells), and monovalent CD3 (T-cells). In NP30179 (NCT03075696), an ongoing multicenter, Phase I dose-escalation expansion study, 0.6–25mg glofitamab fixed-dosing with obinutuzumab pretreatment (Gpt), showed high, durable complete responses manageable safety in heavily pretreated R/R NHL (Dickinson, et al. EHA 2020). step-up dosing (SUD), addition Gpt, allowed dose...
<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>