A5015305870- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Advanced Biosensing Techniques and Applications
- Multiple Myeloma Research and Treatments
- Glycosylation and Glycoproteins Research
- Corneal surgery and disorders
- Chronic Lymphocytic Leukemia Research
- Biosimilars and Bioanalytical Methods
- HER2/EGFR in Cancer Research
- Corneal Surgery and Treatments
- Protein purification and stability
- Radiopharmaceutical Chemistry and Applications
- Ophthalmology and Visual Impairment Studies
- Ocular Surface and Contact Lens
- Vitamin C and Antioxidants Research
- Nanofabrication and Lithography Techniques
- Adrenal Hormones and Disorders
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Intraocular Surgery and Lenses
University Hospital of Wales
2016
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger receptor activation by inducing target clustering and exclusion of CD45 phosphatase from synapse. dimensions molecule play a key role efficiency synapse formation. TDB kills human plasma cells patient-derived at picomolar concentrations results complete depletion bone marrow cynomolgus monkeys. These data...
Abstract Clinical results from the latest strategies for T-cell activation in cancer have fired interest combination immunotherapies that can fully engage immunity. In this study, we describe a trastuzumab-based bispecific antibody, HER2-TDB, which targets HER2 and conditionally activates T cells. HER2-TDB specifically killed HER2-expressing cells at low picomolar concentrations. Because of its unique mechanism action, is independent signaling or chemotherapeutic sensitivity, eliminated...
T cell–dependent bispecific antibodies with bivalent low affinity binding to HER2 are more selective for tumor cells that overexpress the target.
Systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting clinical utility of T cell–redirecting therapies. This study was designed determine how binding affinity for CD3 tumor target HER2 impact efficacy nonclinical safety anti-HER2/CD3 cell–dependent antibodies (TDBs). Affinity found be a major determinant overall tolerability. Higher associated with rapidly elevated peripheral concentrations, weight loss in mice, poor tolerability...
<h3>Purpose</h3> To determine risk factors for the development of acute corneal hydrops in keratoconus UK a case-controlled study. <h3>Methods</h3> Between November 2009 and December 2010, we prospectively identified 73 individuals who developed hydrops. We then 174 controls from nine regions with had not For cases recorded demographics clinical features. Univariate multivariable logistic regressions were performed to identify factors. <h3>Results</h3> analysis suggested strong associations...
Abstract Although CD3-bispecific antibodies have shown promising activity in the treatment of hematological cancers, insufficient T-cell costimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used treating multiple myeloma, possess pleiotropic antimyeloma properties and been described to enhance responses similar costimulatory signaling therefore synergistic effects when combined with bispecifics. In this report, we demonstrate that IMiDs substantially tumor...
Bispecific antibodies are a growing class of therapeutic molecules. Many the current bispecific formats require DNA engineering to convert parental monoclonal into final We describe here method generate molecules from hybridoma IgGs in 3–4 d using chemical conjugation antigen-binding fragments (Fabs) (bisFabs). Proteolytic digestion conditions for each IgG isotype were analyzed optimize yield and quality conjugates. The resulting bisFabs showed no significant amounts homodimers or...
Abstract Ovarian cancer is a diverse class of tumors with very few effective treatment options and suboptimal response rates in early clinical studies using immunotherapies. Here we describe LY6/PLAUR domain containing 1 (LYPD1) as novel target for therapeutic antibodies the ovarian cancer. LYPD1 broadly expressed both primary metastatic ∼70% prevalence serous subset. Bispecific targeting CD3 on T cells tumor antigen have demonstrated significant activity hematologic cancers. We developed an...
<p>Supplementary Data</p>
<p>Supplementary Data</p>
<div>Abstract<p>Although CD3-bispecific antibodies have demonstrated promising activity in the treatment of hematological cancers, insufficient T cell co-stimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used treating multiple myeloma (MM), possess pleiotropic anti-myeloma properties and been described to enhance responses similar co-stimulatory signaling therefore synergistic effects when combined with bispecifics. In this report, we...
Abstract Based on recent clinical success of tumor immunotherapies that block immune suppressive mechanisms to restore T cell function, there is a profound interest in the development targeted therapies. We have produced trastuzumab-based HER2 dependent bispecific antibody (HER2-TDB) conditionally activates cells resulting lysis expressing cancer at low picomolar concentrations. Due its unique mechanism action, which unrelated signaling or sensitivity chemotherapeutic agents, HER2-TDB can...
Abstract Based on the recent clinical success of tumor immunotherapies that block immune suppressive mechanisms to restore T cell function, there is a profound interest in development targeted therapies. We have produced trastuzumab-based HER2 dependent bispecific antibody (HER2/CD3; HER2-TDB; Junttila et al Cancer Res 2014, 74:5561) conditionally activates cells resulting lysis expressing cancer at low picomolar concentrations. In vivo, HER2/CD3 can inhibit growth established mammary tumors...
<p>Supplementary Data</p>
<div>Abstract<p>Although CD3-bispecific antibodies have shown promising activity in the treatment of hematological cancers, insufficient T-cell costimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used treating multiple myeloma, possess pleiotropic antimyeloma properties and been described to enhance responses similar costimulatory signaling therefore synergistic effects when combined with bispecifics. In this report, we demonstrate that IMiDs...
<div>Abstract<p>Although CD3-bispecific antibodies have demonstrated promising activity in the treatment of hematological cancers, insufficient T cell co-stimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used treating multiple myeloma (MM), possess pleiotropic anti-myeloma properties and been described to enhance responses similar co-stimulatory signaling therefore synergistic effects when combined with bispecifics. In this report, we...
<p>Supplementary Data</p>