Abstract
Conditionally replicating adenoviruses (CRAds) represent a promising new platform for anticancer therapy. However, CRAds have been evaluated little in hematopoietic malignancies because of the lack of expression of coxsackie adenovirus receptor (CAR) on their cell surface. In this study, we showed that CAR was expressed on two types of lymphoblastic leukemia cell lines and primary leukemia cells, and that ZD55, a CRAd, exerted a potent antileukemia effect in vitro and in vivo. Furthermore, ZD55 expressing melanoma differentiation-associated gene-7/interleukin-24 (ZD55-IL-24) elicited significant enhanced antileukemia activity comparing with ZD55, concomitant with upregulation of RNA-dependent protein kinase R (PKR), increased phosphorylation of p38 mitogen-activated protein kinase (MAPK), and induction of endoplasmic reticulum (ER) stress. These data for the first time indicate that MDA-7/IL-24 exerts its antitumor effect on leukemia cells via multiple pathways, and suggest that oncolytic adenoviruses, ZD55 and ZD55-IL-24 could potentially be used against CAR-expressing hematological malignancies such as B-lymphoblastic leukemia/lymphoma and some myeloid leukemia.
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Acknowledgements
This work was supported by National Natural Science Foundation of China grants 30470745 (W Qian); 30600257 (Y Tong, W Qian); the Key Social Development Project of Zhejiang Province grants 2004c23005 (W Qian); Chinese National ‘973’ Project Foundation grants 2003AA216031, 2002AA216021 and Natural Science Foundation of China grants 30120160823 (X Liu). We thank L Wang for her help with electron microscope.
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Qian, W., Liu, J., Tong, Y. et al. Enhanced antitumor activity by a selective conditionally replicating adenovirus combining with MDA-7/interleukin-24 for B-lymphoblastic leukemia via induction of apoptosis. Leukemia 22, 361–369 (2008). https://doi.org/10.1038/sj.leu.2405034
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DOI: https://doi.org/10.1038/sj.leu.2405034
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