Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28262555
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by
Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing
#MMPMID28262555
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 JR
; Junttila TT
Cancer Cell
2017[Mar]; 31
(3
): 383-395
PMID28262555
show ga
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.
free
free
free
