Unknown

Dataset Information

0

Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing.


ABSTRACT: 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.

SUBMITTER: Li J 

PROVIDER: S-EPMC5357723 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4022134 | biostudies-literature
| S-EPMC7564331 | biostudies-literature
| S-EPMC2947203 | biostudies-literature
| S-EPMC4875830 | biostudies-literature
| S-EPMC4354371 | biostudies-literature
| S-EPMC6774869 | biostudies-literature
| S-EPMC6770524 | biostudies-literature
| S-EPMC6769613 | biostudies-literature
| S-EPMC5788301 | biostudies-literature
| S-EPMC4282702 | biostudies-literature