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

S Hipp, YT Tai, D Blanset, P Deegen, J Wahl… - Leukemia, 2017 - nature.com
S Hipp, YT Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, PJ Adam, KC Anderson…
Leukemia, 2017nature.com
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 …
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.
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