Thursday, December 12, 2013
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Chimeric Fc g-receptor III
T cells to improve antibody-dependent cell cytotoxicity (ADCC)
Mouse studies suggest T
cells expressing a chimeric receptor that binds to antibody Fc regions could be
used to treat various cancers when combined with antibody therapies. ADCC
results from the engagement of Fc g-receptors expressed
on the surface of NK cells with the Fc regions of tumor cell-bound mAbs. T
cells were engineered to express a chimeric receptor made up of an FCGR3 and
intracellular domains from T cell signaling molecules CD3z and tumor necrosis factor receptor superfamily member 9
(TNFRSF9; 4-1BB; CD137). In a mouse model of
B cell lymphoma, Rituxan rituximab followed
by infusion of the engineered T cells resulted in remission in all 5 mice,
whereas none of 12 mice receiving engineered T cells or Rituxan alone
survived. Similar results occurred in mice bearing neuroblastoma tumors that
received a GD2-targeting mAb followed
by the engineered T cells. Next steps include clinical trials.
Rituxan/MabThera, an antibody
against CD20 from Biogen
Idec Inc. and the Genentech
Inc. unit of Roche,
is marketed for a variety of autoimmune diseases and hematological cancers (see
go universal, page 1).
Published online Dec. 12, 2013
Patent application filed;
available for licensing from the National
University of Singapore and St.
Kudo, K. et al. Cancer
Res.; published online Nov. 6, 2013;
Contact: Dario Campana, National University of Singapore,
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