| Autor: |
Li, J, Stagg, NJ, Johnston, J, Harris, MJ, Menzies, SA, DiCara, D, Clark, V, Hristopoulos, M, Cook, R, Slaga, D, Nakamura, R, McCarty, L, Sukumaran, S, Luis, E, Ye, Z, Wu, TD, Sumiyoshi, T, Danilenko, D, Lee, GY, Totpal, K, Ellerman, D, Hötzel, I, James, Junttila, TT |
| Jazyk: |
angličtina |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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