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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.

Authors :
Yu, Tengteng
Chaganty, Bharat
Lin, Liang
Xing, Lijie
Ramakrishnan, Boopathy
Wen, Kenneth
Hsieh, Phillip A.
Wollacott, Andrew
Viswanathan, Karthik
Adari, Hedy
Cho, Shih-Feng
Li, Yuyin
Chen, Hailin
Yang, Wenjuan
Xu, Yan
An, Gang
Qiu, Lugui
Munshi, Nikhil
Babcock, Gregory
Shriver, Zachary
Source :
Blood Cancer Journal; Nov2020, Vol. 10 Issue 11, p1-13, 13p
Publication Year :
2020

Abstract

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 < 0.0001), and rapidly eradicated myeloma burden in all mice concomitantly receiving bortezomib, with 100% host survival. Taken together, these data strongly support clinical development of VIS832, alone and in combination, for the therapeutic treatment of MM in relapsed and refractory patients while pointing to its potential therapeutic use earlier in disease intervention. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20445385
Volume :
10
Issue :
11
Database :
Complementary Index
Journal :
Blood Cancer Journal
Publication Type :
Academic Journal
Accession number :
147702725
Full Text :
https://doi.org/10.1038/s41408-020-00378-z