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2017 ; 8
(15
): 24046-24062
Nephropedia Template TP
gab.com Text
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English Wikipedia
PSMA-homing dsRNA chimeric protein vector kills prostate cancer cells and
activates anti-tumor bystander responses
#MMPMID28445962
Langut Y
; Edinger N
; Flashner-Abramson E
; Melamed-Book N
; Lebendiker M
; Levi-Kalisman Y
; Klein S
; Levitzki A
Oncotarget
2017[Apr]; 8
(15
): 24046-24062
PMID28445962
show ga
The treatment of metastatic androgen-resistant prostate cancer remains a
challenge. We describe a protein vector that selectively delivers synthetic
dsRNA, polyinosinic/polycytidylic acid (polyIC), to prostate tumors by targeting
prostate specific membrane antigen (PSMA), which is overexpressed on the surface
of prostate cancer cells.The chimeric protein is built from the double stranded
RNA (dsRNA) binding domain of PKR tethered to a single chain anti-PSMA antibody.
When complexed with polyIC, the chimera demonstrates selective and efficient
killing of prostate cancer cells. The treatment causes the targeted cancer cells
to undergo apoptosis and to secrete toxic cytokines. In a "bystander effect",
these cytokines kill neighboring cancer cells that do not necessarily overexpress
PSMA, and activate immune cells that enhance the killing effect. The strong
effects of the targeted polyIC are demonstrated on both 2D cell cultures and 3D
tumor spheroids.