Bevacizumab Increases Viral Distribution in Human Anaplastic Thyroid Carcinoma Xenografts and Enhances the Effects of E1A-Defective Adenovirus d/922-947

Purpose: Anaplastic thyroid carcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms and is refractory to conventional treatments such as chemotherapy and radiotherapy.We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus d/922-947. Experimental Design: The antitumor efficacies of the E1A Delta CR2 (d/922-947) and Delta E1B55K (d/1520) mutants were compared in human thyroid anaplastic carcinoma cells in culture and in xenografts in vivo, To enhance the effects of d/922-947, anaplastic thyroid carcinoma tumor xenografts were treated with d/922-947 in combination with bevacizumab. Results: We showed that the efficacy of d/922-947 exceeded that of d/1520 in all tested anaplastic thyroid carcinoma cells in vitro and in vivo. Furthermore, bevacizumab in combination with d/922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improved viral distribution in neoplastic tissues. Conclusions: Our data showed that d/922-947 had a higher oncolytic activity compared with d/1520 in anaplastic thyroid carcinoma cell lines and might represent a better option for virotherapy of anaplastic thyroid carcinoma. Moreover, bevacizumab increased the oncolytic effects of d/922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the d/922-947 virus in combination with bevacizumab.