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2016 ; 7
(50
): 83392-83408
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
CD19-specific triplebody SPM-1 engages NK and ?? T cells for rapid and efficient
lysis of malignant B-lymphoid cells
#MMPMID27825135
Schiller CB
; Braciak TA
; Fenn NC
; Seidel UJ
; Roskopf CC
; Wildenhain S
; Honegger A
; Schubert IA
; Schele A
; Lämmermann K
; Fey GH
; Jacob U
; Lang P
; Hopfner KP
; Oduncu FS
Oncotarget
2016[Dec]; 7
(50
): 83392-83408
PMID27825135
show ga
Triplebodies are antibody-derived recombinant proteins carrying 3 antigen-binding
domains in a single polypeptide chain. Triplebody SPM-1 was designed for lysis of
CD19-bearing malignant B-lymphoid cells through the engagement of CD16-expressing
cytolytic effectors, including NK and ?? T cells.SPM-1 is an optimized version of
triplebody ds(19-16-19) and includes humanization, disulfide stabilization and
the removal of potentially immunogenic sequences. A three-step chromatographic
procedure yielded 1.7 - 5.5 mg of purified, monomeric protein per liter of
culture medium. In cytolysis assays with NK cell effectors, SPM-1 mediated potent
lysis of cancer-derived B cell lines and primary cells from patients with various
B-lymphoid malignancies, which surpassed the ADCC activity of the therapeutic
antibody Rituximab. EC50-values ranged from 3 to 86 pM. Finally, in an
impedance-based assay, SPM-1 mediated a particularly rapid lysis of CD19-bearing
target cells by engaging and activating both primary and expanded human ?? T
cells from healthy donors as effectors.These data establish SPM-1 as a useful
tool for a kinetic analysis of the cytolytic reactions mediated by ?? T and NK
cells and as an agent deserving further development towards clinical use for the
treatment of B-lymphoid malignancies.