Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.60 (
caspase-7
)
920
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We report here a novel strategy to redirect oncolytic adenoviruses to CD123 by carry a soluble coxsackie-adenovirus receptor (sCAR)-
IL3
expression cassette in the viral genome to form Ad.
IL3
, which sustainably infected acute myeloid leukemia (AML) cells through CD123. Ad.
IL3
was further engineered to harbor gene encoding manganese superoxide dismutase (MnSOD) or mannose-binding plant lectin Pinellia pedatisecta agglutinin (PPA), forming Ad.
IL3
-MnSOD and Ad.
IL3
-PPA. As compared with Ad.
IL3
or Ad.sp-E1A control, Ad.
IL3
-MnSOD and Ad.
IL3
-PPA significantly suppressed in vitro proliferation of HL60 and KG-1 cells. Elevated apoptosis was detected in HL60 and KG-1 cells treated with either Ad.
IL3
-MnSOD or Ad.
IL3
-PPA. The caspase-9-
caspase-7
pathway was determined to be activated by Ad.
IL3
-MnSOD as well as by Ad.
IL3
-PPA in HL60 cells. In an HL60/Luc xenograft nonobese diabetic/severe-combined immunodeficiency mice model, Ad.
IL3
-MnSOD and Ad.
IL3
-PPA suppressed cancer cell growth as compared with Ad.
IL3
. A significant difference of cancer cell burden was detected between Ad.
IL3
and Ad.
IL3
-PPA groups at day 9 after treatment. Furthermore, Ad.
IL3
-MnSOD significantly prolonged mouse survival as compared with Ad.sp-E1A. These findings demonstrated that Ad.
IL3
-gene could serve as a novel agent for AML therapy. Harboring sCAR-ligand expression cassette in the viral genome may provide a universal method to redirect oncolytic adenoviruses to various membrane receptors on cancer cells resisting serotype 5 adenovirus infection.
...
PMID:CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell proliferation in vitro and in vivo. 2465 72
