Oncolytic adenovirus armed with IL-24 inhibits the growth of breast cancer in vitro and in vivo.
BACKGROUND
Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy.


METHODS
A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24) was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor.


RESULTS
We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon was observed in the metastatic model achieved by left ventricular injection as suggested by in vivo luminescence imaging of tumor growth.


CONCLUSIONS
The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Wei
W
Zhu
Lai
L
Wei
Hongwei
H
Zhang
Junxue
J
Chen
Xinyu
X
Qin
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D007378:Interleukins; D011994:Recombinant Proteins; D000099180:Interleukin-24