A5025250615- Peptidase Inhibition and Analysis
- Inflammatory mediators and NSAID effects
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Click Chemistry and Applications
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Neuropeptides and Animal Physiology
- Radiopharmaceutical Chemistry and Applications
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Systemic Lupus Erythematosus Research
- Nanoplatforms for cancer theranostics
- Cell Image Analysis Techniques
- Salivary Gland Disorders and Functions
Roche Pharma AG (Germany)
2012-2018
Idorsia (Switzerland)
2018
Actelion (Switzerland)
2015
Roche (Switzerland)
2010-2014
CS Diagnostics
2011
Depletion of immunosuppressive tumor-associated macrophages (TAMs) or reprogramming toward a proinflammatory activation state represent different strategies to therapeutically target this abundant myeloid population. In study, we report that inhibition colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAMs profound and rapid in the presence CD40 agonist before their depletion. Despite short-lived nature macrophage hyperactivation, combined CSF-1R+CD40 stimulation is...
Abstract Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation disease progression. Therefore, the development agents that overcome dysregulation in tumor cells is an attractive therapeutic approach. Activation extrinsic apoptotic pathway strongly dependent on receptor (DR) hyperclustering surface. However, strategies activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue alternative approach for...
The epidermal growth factor receptor (EGFR) and the insulin-like factor-1 (IGF-1R) play critical roles in tumor growth, providing a strong rationale for combined inhibition of IGF-1R EGFR signaling cancer therapy. We describe design, affinity maturation, vitro vivo characterization bispecific anti-IGF-1R/EGFR antibody XGFR*. XGFR* is based on IgG XGFR, which enabled heterodimerization an binding scFab heavy chain with EGFR-binding light by "knobs-into-holes" technology. optimized monovalent...
The tumour-modulating effects of the endogenous adaptive immune system are rather paradoxical. Whereas some clinical and experimental observations offer compelling evidence for existence immunosurveillance, other studies have revealed promoting on primary cancer development metastatic disease. We examined functional significance as a regulator spontaneous HER2(+) breast tumourigenesis pulmonary metastasis formation, using MMTV-NeuT mouse model in which mammary carcinogenesis is induced by...
Abstract Background: Activation of the extrinsic apoptosis pathway in tumor cells through agonistic death receptor 5 (DR5) antibodies has been evaluated clinic with limited success so far. In this context, several reports show that DR5 activation is strongly dependent on hyperclustering cell surface. Therefore a therapeutic principle induces specifically at site may provide superior efficacy, potency and safety compared to conventional antibodies. Fibroblast protein (FAP) marker for...
Abstract Background: Elevated signaling via the receptor tyrosine kinases IGF-1R and EGFR has been identified as common characteristic of multiple cancer type. signal predominantly through PI3K MAPK pathways thereby mediate growth survival signals crucial for development progression cancer. There is strong cross talk on levels between dependent pathways. Therefore, targeting simultaneously an attractive way to achieve maximal inhibition transduction avoid resistance formation. Methods:...
Abstract Myeloid cells represent the most abundant immune cell type within tumor microenvironment of certain entities, including associated macrophages (TAMs). Macrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. The major survival for TAMs is macrophage colony stimulating 1 (CSF1). We generated a monoclonal antibody (RG7155) that binds to secondary dimerization interface CSF1 receptor (CSF1R) specific and potent allosteric inhibitor....
Abstract Background: Activation of the extrinsic apoptotic pathway by TRAIL is dependent on clustering death receptors (DR) surface cells. However, current TRAIL-based strategies have proven ineffective in and failed to demonstrate robust therapeutic activity clinical trials. More potent DR agonist therapies could help overcome insufficient activation resistance activation. RG7386 a novel bispecific FAP-DR5 antibody, binding with high affinity fibroblast protein (FAP) low DR5. FAP expressed...
Abstract Background: Activation of the extrinsic apoptosis pathway in tumor cells through agonistic death receptor 5 (DR5) antibodies has been evaluated clinic with limited success so far. In this context, several reports show that DR5 activation is strongly dependent on hyperclustering cell surface. Therefore a therapeutic principle induces specifically at site may provide superior efficacy, potency and safety compared to conventional antibodies. Fibroblast protein (FAP) marker for...
Abstract Background This is the first study performing a head to comparison of monoclonal IGF-1R antibodies (mAb) based on published sequences for therapeutic mAbs from Pfizer (CP751,871, IgG2 kappa), Amgen (AMG479, IgG1 lambda), Merck (h7C10, cloned R1507 backbone), Imclone (IMC-A12, lambda) and Roche (R1507, IgG1). Methods In this study, sequence information was extracted patents used clone transiently express IgGs (*=re-synthesized) in HEK293F cells. vitro assays ligand binding,...
<div>Abstract<p>Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation disease progression. Therefore, the development agents that overcome dysregulation in tumor cells is an attractive therapeutic approach. Activation extrinsic apoptotic pathway strongly dependent on receptor (DR) hyperclustering surface. However, strategies activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue alternative...
<p>Figure S1. Related to Figure 1. Characterization of FAP-drozitumab BsAbs and antitumor efficacy in the presence FAP-expressing fibroblasts vitro co-culture models; Table BsAb binding DR5 FAP antigens; S2. Anti-tumor bispecific molecules is FAPdependent.</p>
<p>FAP-drozitumab BsAb induces tumor growth inhibition in vivo.</p>
<p>Characterization and optimization of RG7386 dosing in vivo.</p>
<p>Supplementary information on cell maintenance, and antibody selection characterization</p>
<p>Figure S2. Related to Figure 3. In vitro characterization of the FAP-DR5 BsAb RG7386; Table S4. Characterization RG7386 binding avidities.</p>
<p>Figure S1. Related to Figure 1. Characterization of FAP-drozitumab BsAbs and antitumor efficacy in the presence FAP-expressing fibroblasts vitro co-culture models; Table BsAb binding DR5 FAP antigens; S2. Anti-tumor bispecific molecules is FAPdependent.</p>
<p>FAP-drozitumab BsAb induces tumor growth inhibition in vivo.</p>