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A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Authors :
Hipp, S
Tai, Y-T
Blanset, D
Deegen, P
Wahl, J
Thomas, O
Rattel, B
Adam, P J
Anderson, K C
Friedrich, M
Source :
Leukemia; August 2017, Vol. 31 Issue: 8 p1743-1751, 9p
Publication Year :
2017

Abstract

B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.

Details

Language :
English
ISSN :
08876924 and 14765551
Volume :
31
Issue :
8
Database :
Supplemental Index
Journal :
Leukemia
Publication Type :
Periodical
Accession number :
ejs42886351
Full Text :
https://doi.org/10.1038/leu.2016.388