Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma

Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)- 18(ZD55-IL- 18) and dacarbazine(DTIC) against melanoma. Melanoma A375 cells or nude mousetumor xenografts were treated with ZD55-IL- 18alone or together with DTIC. The results showed that ZD55-IL- 18competently replicated in A375 cells and expressed IL- 18, and these were not affected by DTIC. ZD55-IL- 18enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL- 18and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL- 18and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.