Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus d/922-947

Purpose: Anaplastic thyroidcarcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms andis refractory to conventional treatments such as chemotherapy andradiotherapy.We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl 922-947. Experimental Design: The antitumor efficacies of the E1AδCR2 (dl922-947) and AE1B55K (dl1520) mutants were comparedin human thyroid anaplastic carcinoma cells in culture andin xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroidcarcinoma tumor xenografts were treatedwith dl922-947 in combination with bevacizumab. Results: We showedthat the efficacy of dl922-947 exceeded that of dl1520 in all testedana-plastic thyroidcarcinoma cells in vitro and in vivo.Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improvedviral distribution in neoplastic tissues. Conclusions: Our data showed that dl922-947 hada higher oncolytic activity compared with dl1520 in anaplastic thyroidcarcinoma cell lines andmight represent a better option for virother-apy of anaplastic thyroidcarcinoma. Moreover, bevacizumab increasedthe oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.