Development of a New BCMAxCD3 Duobody® Antibody for Multiple Myeloma
| العنوان: | Development of a New BCMAxCD3 Duobody® Antibody for Multiple Myeloma |
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| المؤلفون: | Nate Majewski, Ricardo Attar, Kevin Bellew, Mark Mendonca, Francois Gaudet, Alexander Babich, Leopoldo Luistro, Linda Barone, Yingzhe Li, Eric Baldwin, Kodandaram Pillarisetti, Xiaochun Zhang, Yusri Elsayed, Rupesh Nanjunda, Diana Chin, Stephen I. Rudnick |
| المصدر: | Blood. 128:2116-2116 |
| بيانات النشر: | American Society of Hematology, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, T cell, Immunology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Antigen, medicine, B-cell activating factor, biology, business.industry, Cell Biology, Hematology, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, biology.protein, Tumor necrosis factor alpha, Bone marrow, Antibody, business, Monoclonal gammopathy of undetermined significance |
| الوصف: | B-cell maturation antigen (BCMA) is a tumor necrosis factor (TNF) family surface protein predominantly expressed on terminally differentiated B-cells. BCMA signals through P38/NF-κB pathway upon binding to its ligands; a proliferation inducing ligand (APRIL) and B-cell activator of the TNF family (BAFF) and promote anti-apoptotic gene expression. BCMA expression is elevated in plasma blasts, plasma cells from spleen and bone marrow and correlates with disease progression in multiple myeloma (MM). BCMA expression in premalignant MM settings such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) also gives an opportunity for early cancer interception. To target cancer cells expressing BCMA, we developed a BCMAxCD3 bispecific antibody using the Genmab DuoBody® technology (Ab-957) to recruit T cells to BCMA-expressing MM cells so that T cells could be activated and induced to kill BCMA+ cancer cells. This antibody can induce cytotoxicity of BCMA+ MM cell lines in vitro (H929 cells: EC50=0.15nM, MM1.R cells: EC50=0.06nM, RPMI8226 cells: EC50=0.45nM) with a concomitant T cell activation (H929 cells: EC50=0.21nM, MM1.R cells: EC50=0.1nM, RPMI8226 cells: EC50=0.28nM). In contrast, this antibody was unable to kill BCMA- cancer cell line (MV4-11), demonstrating the specificity of the cytotoxicity. Ab-957 also inhibited tumor development or growth in two BCMA+ MM murine xenograft models inoculated with human T cells. Furthermore, this antibody could deplete BCMA+ cells in bone marrow samples from MM patient's in an ex-vivo assay with an average EC50 value of 2.5 nM. Lastly, Ab-957 is well-tolerated in cynomolgus monkey and is being developed for Phase I clinical trial in patients with multiple myeloma. Disclosures Pillarisetti: Janssen: Employment. Baldwin:Janssen: Employment. Babich:Janssen: Employment. Majewski:Janssen: Employment. Barone:Janssen: Employment. Li:Janssen: Employment. Zhang:Janssen: Employment. Chin:Janssen: Employment. Luistro:Janssen: Employment. Mendonça:Janssen: Employment. Nanjunda:Janssen: Employment. Rudnick:Janssen Pharmaceuticals R&D: Employment. Bellew:Janssen: Employment. Elsayed:Janssen: Employment, Other: stock options. Attar:Janssen: Employment. Gaudet:Janssen Pharmaceuticals R&D: Employment, Other: Stock options, Patents & Royalties: pending, not yet issued. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::64f1c04cb43bc6cc2ae69dea04c354e9 https://doi.org/10.1182/blood.v128.22.2116.2116 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........64f1c04cb43bc6cc2ae69dea04c354e9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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