A5048842300- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Nanoparticle-Based Drug Delivery
- Radiopharmaceutical Chemistry and Applications
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- 14-3-3 protein interactions
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- Advanced Biosensing Techniques and Applications
- Protein purification and stability
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Neuroblastoma Research and Treatments
- Prostate Cancer Treatment and Research
- Biosimilars and Bioanalytical Methods
MacroGenics (United States)
2009-2023
Amgen (United States)
2009
The goal of this research was to harness a monoclonal antibody (mAb) discovery platform identify cell-surface antigens highly expressed on cancer and develop, through Fc optimization, potent mAb therapies toward these tumor-specific antigens.Fifty independent mAbs targeting the immunoregulatory B7-H3 protein were obtained intact cell-based immunizations using human tissue progenitor cells, cell lines, or lines displaying stem properties. Binding studies revealed natively reactive panel bind...
Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety activity in phase 1 dose-escalation cohort-expansion trial patients with solid tumors or hematologic malignancies disease progression on previous treatment. Primary endpoints were maximum tolerated dose of tebotelimab when administered as single agent (n = 269) combination the anti-HER2 antibody margetuximab 84). Secondary included anti-tumor activity. In advanced cancer...
B7-H3, also referred to as CD276, is a member of the B7 family immune regulatory proteins. B7-H3 overexpressed on many solid cancers, including prostate cancer, renal cell carcinoma, melanoma, squamous carcinoma head and neck, non-small lung breast cancer. Overexpression associated with disease severity, risk recurrence reduced survival. In this article, we report preclinical development MGC018, an antibody-drug conjugate targeted against B7-H3. MGC018 comprised cleavable linker-duocarmycin...
We have developed MGD007 (anti-glycoprotein A33 x anti-CD3), a DART protein designed to redirect T cells target gpA33 expressing colon cancer. The was selected on the basis of an antibody-based screen identify cancer antigens universally expressed in both primary and metastatic colorectal specimens, including putative stem cell populations. displays anticipated-bispecific binding properties mediates potent lysis gpA33-positive lines, models cells, through recruitment cells. Xenograft studies...
Abstract ADAM metallopeptidase domain 9 (ADAM9) is a member of the family multifunctional, multidomain type 1 transmembrane proteins. ADAM9 overexpressed in many cancers, including non–small cell lung, pancreatic, gastric, breast, ovarian, and colorectal cancer, but exhibits limited expression normal tissues. A target-unbiased discovery platform based on intact tumor progenitor immunizations, followed by an IHC screen, led to identification anti-ADAM9 antibodies with selective...
Abstract Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 recognized by the RAV12 monoclonal antibody. binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward tumor xenografts. Objective.—To determine expression pattern of normal tissue identify indications for clinical study potential safety...
Abstract Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 recognized by the RAV12 monoclonal antibody. binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward tumor xenografts. Objective.—To determine expression pattern of normal tissue identify indications for clinical study potential safety...
Abstract ADAM9, also known as MDC9 or meltrin-γ, is a member of the ADAM (a disintegrin and metalloproteinase) family proteases, which have been implicated in cytokine growth factor shedding, cell migration. Dysregulation ADAM9 has tumor progression metastasis, well pathological neovascularization. overexpression shown to correlate with poor prognosis prostate, renal, pancreatic cancers. Using an immunization approach antibodies were raised fetal progenitor stem-like cancer lines followed by...
Abstract Introduction: Monoclonal antibodies (mAbs) were generated via a target-unbiased approach based on intact cell immunization with lines, fetal progenitor cells, and cancer stem cells. An immunohistochemical screen for cancer-specific candidates identified panel of anti-B7-H3 (CD276) mAbs highly differential tumor-versus-normal tissue binding. B7-H3 expression was observed in tumor epithelium as well tumor-associated vasculature stroma. Consistent our findings, has been reported to be...
Abstract Introduction: Prostate cancer is the second most common among men worldwide. In 2021, it estimated that 248,530 in United States will be diagnosed with prostate cancer, and 34,130 die from disease. Although current treatments have success initially, development of resistance commonly leads to recurrence an incurable castrate-resistant form Thus, significant need for novel therapies improve outcome remains. B7-H3 (CD276), a member B7 family immunomodulatory molecules, overexpressed...
<p>PDF file, 78KB, Measurement of the absolute level circulating B cells (CD20+; Panel A), T (CD3+; B) and NK (CD159a+)Panel C) in blood samples collected from cynomolgus monkeys at indicated days prior to administration (Day -2), or following intravenous PBS vehicle on Day 1 (all animals received 1) MGA271 8 dose. The panels left for each group represent all (N=6) dosing group, while right only recovery (N=2) group.</p>
<p>PDF file, 75KB, Expression level of B7-H3 on ATCC cancer cell lines as determined by FLOW cytometry with anti-B7-H3 mAb BRCA84D. Solid curves represent isotype control staining; open staining FI.</p>
<p>PDF file, 78KB.</p>
<p>PDF file, 89KB, Measurement of IL-5 (Panel A), IL-6 B) and TNF-B C) cytokine levels in serum samples collected from cynomolgus monkeys prior to infusion (Pre) or at the indicated time points following intravenous administration PBS vehicle (Day 1) MGA271 dose 8). The top two panels each data set represent all animals (N=6) dosing group, while bottom three only recovery group (N=2) group. Sera were analyzed for using Becton Dickinson Cytometric Bead Array Non-Human Primate Th1/Th2...
<p>PDF file, 204KB, Panel A: Representative reactivity of anti-B7-H3 mAb BRCA84D with frozen tissue sections prostate, breast, colon, lung, gastric and renal cancer. B: Reactivity BRCA69D on formalin-fixed paraffin embedded normal human spleen lymph node tissues.</p>
<p>PDF file, 78KB.</p>
<p>PDF file, 89KB, Measurement of IL-5 (Panel A), IL-6 B) and TNF-B C) cytokine levels in serum samples collected from cynomolgus monkeys prior to infusion (Pre) or at the indicated time points following intravenous administration PBS vehicle (Day 1) MGA271 dose 8). The top two panels each data set represent all animals (N=6) dosing group, while bottom three only recovery group (N=2) group. Sera were analyzed for using Becton Dickinson Cytometric Bead Array Non-Human Primate Th1/Th2...
<p>PDF file, 78KB, Measurement of the absolute level circulating B cells (CD20+; Panel A), T (CD3+; B) and NK (CD159a+)Panel C) in blood samples collected from cynomolgus monkeys at indicated days prior to administration (Day -2), or following intravenous PBS vehicle on Day 1 (all animals received 1) MGA271 8 dose. The panels left for each group represent all (N=6) dosing group, while right only recovery (N=2) group.</p>
<p>PDF file, 204KB, Panel A: Representative reactivity of anti-B7-H3 mAb BRCA84D with frozen tissue sections prostate, breast, colon, lung, gastric and renal cancer. B: Reactivity BRCA69D on formalin-fixed paraffin embedded normal human spleen lymph node tissues.</p>
<p>PDF file, 75KB, Expression level of B7-H3 on ATCC cancer cell lines as determined by FLOW cytometry with anti-B7-H3 mAb BRCA84D. Solid curves represent isotype control staining; open staining FI.</p>
<div>Abstract<p><b>Purpose:</b> The goal of this research was to harness a monoclonal antibody (mAb) discovery platform identify cell-surface antigens highly expressed on cancer and develop, through Fc optimization, potent mAb therapies toward these tumor-specific antigens.</p><p><b>Experimental Design:</b> Fifty independent mAbs targeting the immunoregulatory B7-H3 protein were obtained intact cell-based immunizations using human tissue...