Ant
igen
ic modulat
ion by trogocytos
is dur
ing ant
i-CD20 mAb treatment w
ith r
itux
imab (RTX) leads to loss of CD20 and therefore can comprom
ise therapy. Dur
ing trogocytos
is, effector cells, such as macrophages, remove CD20 from the surface of ant
ibody-coated cells
in an Fc receptor-dependent manner. Importantly, Fc¦Ã receptors (Fc¦ÃRs) are also cruc
ial
in the ant
i-tumor effects of RTX by
induc
ing ant
ibody dependent cell-med
iated cytotox
ic
ity (ADCC). Here we stud
ied the role of Fc¦ÃR dur
ing RTX-
induced trogocytos
is of CD20
in an
intraper
itoneal tumor model w
ith EL4-CD20 cells. We found marked RTX-
induced trogocytos
is of CD20
in Fc¦ÃRI- or Fc¦ÃRIII-def
ic
ient m
ice, s
im
ilar to w
ild type m
ice, demonstrat
ing a redundancy for act
ivat
ing Fc¦ÃR
in trogocytos
is. Interest
ingly,
in FcR¦Ã-cha
in-def
ic
ient m
ice, trogocytos
is was st
ill apparent,
ind
icat
ing that the
inh
ib
itory receptor Fc¦ÃRIIB alone can also med
iate trogocytos
is. These data were conf
irmed by
in vitro analys
is w
ith block
ing ant
ibod
ies. Decreas
ing the amount of RTX
in vivo resulted
in less trogocytos
is of CD20, support
ing cl
in
ical stud
ies w
ith lower RTX dose. Importantly, we show that cells wh
ich undergo
in vivo trogocytos
is can st
ill be k
illed
ex vivo by ADCC but not by complement-med
iated cytotox
ic
ity (CDC), underscor
ing the cl
in
ical relevance of trogocytos
is.
Taken together, our study provides more insights into the mechanism and consequences of RTX-induced trogocytosis of CD20.