期刊
CANCER CELL
卷 31, 期 3, 页码 383-395出版社
CELL PRESS
DOI: 10.1016/j.ccell.2017.02.001
关键词
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资金
- Sir Henry Dale Fellowship - Wellcome Trust [099966/Z/12/Z]
- Sir Henry Dale Fellowship - Royal Society [099966/Z/12/Z]
- Wellcome Trust [102195/Z/13/Z]
- Wellcome Trust [099966/Z/12/Z, 102195/Z/13/Z] Funding Source: Wellcome Trust
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.
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