VIS832, a novel CD138-targeting monoclonal antibody, potently induces killing of human multiple myeloma and further synergizes with IMiDs or bortezomib in vitro and in vivo
| Autor: | Yan Xu, Phillip A Hsieh, Gang An, Hedy Adari, Kenneth C. Anderson, Yuyin Li, Zachary Shriver, Kenneth Wen, Lijie Xing, Lugui Qiu, Gregory J. Babcock, James R. Myette, Liang Lin, Andrew M. Wollacott, Bharat Chaganty, Boopathy Ramakrishnan, Hailin Chen, Wenjuan Yang, Karthik Viswanathan, Nikhil C. Munshi, Shih-Feng Cho, Yu-Tzu Tai, Tengteng Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Indatuximab ravtansine
Immunoconjugates medicine.drug_class Mice SCID Monoclonal antibody lcsh:RC254-282 Article Bortezomib Mice Antineoplastic Agents Immunological Targeted therapies Antigen In vivo immune system diseases hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans Maytansine Multiple myeloma Lenalidomide Cancer business.industry Daratumumab Drug Synergism Hematology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Xenograft Model Antitumor Assays Neoplasm Proteins Oncology Cancer research Syndecan-1 business Multiple Myeloma medicine.drug |
| Zdroj: | Blood Cancer Journal Blood Cancer Journal, Vol 10, Iss 11, Pp 1-13 (2020) |
| ISSN: | 2044-5385 |
| Popis: | Therapeutically targeting CD138, a define multiple myeloma (MM) antigen, is not yet approved for patients. We here developed and determined the preclinical efficacy of VIS832, a novel therapeutic monoclonal antibody (MoAb) with differentiated CD138 target binding to BB4 that is anti-CD138 MoAb scaffold for indatuximab ravtansine (BT062). VIS832 demonstrated enhanced CD138-binding avidity and significantly improved potency to kill MM cell lines and autologous patient MM cells regardless of resistance to current standard-of-care therapies, via robust antibody-dependent cellular cytotoxicity and phagocytosis mediated by NK and macrophage effector cells, respectively. Specifically, CD38-targeting daratumumab-resistant MM cells were highly susceptible to VIS832 which, unlike daratumumab, spares NK cells. Superior maximal cytolysis of VIS832 vs. daratumumab corresponded to higher CD138 vs. CD38 levels in MM cells. Furthermore, VIS832 acted synergistically with lenalidomide or bortezomib to deplete MM cells. Importantly, VIS832 at a sub-optimal dose inhibited disseminated MM1S tumors in vivo as monotherapy (P |
| Databáze: | OpenAIRE |
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