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 dl922-947. EXPERIMENTAL DESIGN: The antitumor efficacies of the E1ADeltaCR2 (dl922-947) and DeltaE1B55K (dl1520) mutants were compared in human thyroid anaplastic carcinoma cells in culture and in xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroid carcinoma tumor xenografts were treated with dl922-947 in combination with bevacizumab. RESULTS: We showed that the efficacy of dl922-947 exceeded that of dl1520 in all tested anaplastic thyroid carcinoma 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 improved viral distribution in neoplastic tissues. CONCLUSIONS: Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 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 dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.
PURPOSE:Anaplastic thyroid carcinoma is a prime target for innovative therapy because it represents one of the most lethal humanneoplasms 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 dl922-947. EXPERIMENTAL DESIGN: The antitumor efficacies of the E1ADeltaCR2 (dl922-947) and DeltaE1B55K (dl1520) mutants were compared in humanthyroid anaplastic carcinoma cells in culture and in xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroid carcinomatumor xenografts were treated with dl922-947 in combination with bevacizumab. RESULTS: We showed that the efficacy of dl922-947 exceeded that of dl1520 in all tested anaplastic thyroid carcinoma 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 improved viral distribution in neoplastic tissues. CONCLUSIONS: Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 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 dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.
Authors: Wei Zhang; Giulia Fulci; Jason S Buhrman; Anat O Stemmer-Rachamimov; John W Chen; Gregory R Wojtkiewicz; Ralph Weissleder; Samuel D Rabkin; Robert L Martuza Journal: Mol Ther Date: 2011-09-13 Impact factor: 11.454
Authors: Mark A Currier; Francis K Eshun; Allyson Sholl; Artur Chernoguz; Kelly Crawford; Senad Divanovic; Louis Boon; William F Goins; Jason S Frischer; Margaret H Collins; Jennifer L Leddon; William H Baird; Amy Haseley; Keri A Streby; Pin-Yi Wang; Brett W Hendrickson; Rolf A Brekken; Balveen Kaur; David Hildeman; Timothy P Cripe Journal: Mol Ther Date: 2013-03-12 Impact factor: 11.454
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Authors: Daniel Oberg; Eva Yanover; Virginie Adam; Katrina Sweeney; Celina Costas; Nick R Lemoine; Gunnel Halldén Journal: Clin Cancer Res Date: 2010-01-12 Impact factor: 12.531