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

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