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2017 ; 8
(35
): 57964-57980
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
CD3xPDL1 bi-specific T cell engager (BiTE) simultaneously activates T cells and
NKT cells, kills PDL1(+) tumor cells, and extends the survival of tumor-bearing
humanized mice
#MMPMID28938530
Horn LA
; Ciavattone NG
; Atkinson R
; Woldergerima N
; Wolf J
; Clements VK
; Sinha P
; Poudel M
; Ostrand-Rosenberg S
Oncotarget
2017[Aug]; 8
(35
): 57964-57980
PMID28938530
show ga
Bi-specific T cell engagers (BiTEs) activate T cells through CD3 and target
activated T cells to tumor-expressed antigens. BiTEs have shown therapeutic
efficacy in patients with liquid tumors; however, they do not benefit all
patients. Anti-tumor immunity is limited by Programmed Death 1 (PD1)
pathway-mediated immune suppression, and patients who do not benefit from
existing BiTES may be non-responders because their T cells are anergized via the
PD1 pathway. We have designed a BiTE that activates and targets both T cells and
NKT cells to PDL1(+) cells. In vitro studies demonstrate that the CD3xPDL1 BiTE
simultaneously binds to both CD3 and PDL1, and activates healthy donor CD4(+) and
CD8(+) T cells and NKT cells that are specifically cytotoxic for PDL1(+) tumor
cells. Cancer patients' PBMC are also activated and cytotoxic, despite the
presence of myeloid-derived suppressor cells. The CD3xPDL1 BiTE significantly
extends the survival time and maintains activated immune cell levels in humanized
NSG mice reconstituted with human PBMC and carrying established human melanoma
tumors. These studies suggest that the CD3xPDL1 BiTE may be efficacious for
patients with PDL1(+) solid tumors, in combination with other immunotherapies
that do not specifically neutralize PD1 pathway-mediated immune suppression.