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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunol
2018 ; 200
(7
): 2304-2312
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The PI3K?-Selective Inhibitor Idelalisib Minimally Interferes with Immune
Effector Function Mediated by Rituximab or Obinutuzumab and Significantly
Augments B Cell Depletion In Vivo
#MMPMID29453281
Palazzo A
; Herter S
; Grosmaire L
; Jones R
; Frey CR
; Limani F
; Bacac M
; Umana P
; Oldham RJ
; Marshall MJE
; Cox KL
; Turaj AH
; Cragg MS
; Klein C
; Carter MJ
; Tannheimer S
J Immunol
2018[Apr]; 200
(7
): 2304-2312
PMID29453281
show ga
Idelalisib is a highly selective oral inhibitor of PI3K? indicated for the
treatment of patients with relapsed chronic lymphocytic leukemia in combination
with rituximab. Despite additive clinical effects, previous studies have
paradoxically demonstrated that targeted therapies potentially negatively affect
anti-CD20 mAb effector mechanisms. To address these potential effects, we
investigated the impact of PI3K? inhibition by idelalisib on the effector
mechanisms of rituximab and obinutuzumab. At clinically relevant concentrations,
idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent
cellular cytotoxicity and phagocytosis on human lymphoma cell lines, while
maintaining the superiority of obinutuzumab-mediated Ab-dependent cellular
cytotoxicity. Consistent with this, idelalisib did not influence
obinutuzumab-mediated B cell depletion in whole-blood B cell-depletion assays.
Further, idelalisib significantly enhanced obinutuzumab-mediated direct cell
death of chronic lymphocytic leukemia cells. In murine systems, in vivo
inhibition of PI3K? minimally interfered with maximal rituximab- or
obinutuzumab-mediated depletion of leukemic targets. In addition, the duration of
rituximab- and obinutuzumab-mediated depletion of leukemia cells was extended by
combination with PI3K? inhibition. Collectively, these data demonstrate that
PI3K? inhibition does not significantly affect the effector mechanisms induced by
rituximab or obinutuzumab and provides an effective in vivo therapeutic
combination. Therefore, combinations of obinutuzumab and idelalisib are currently
being assessed in clinical studies.