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ONYX-015, an E1B Gene-Defective Adenovirus, Induces Cell Death in Human Anaplastic Thyroid Carcinoma Cell Lines

Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia Università di Napoli Federico II, and Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, 80131 Naples, Italy

Address all correspondence and requests for reprints to: Dr. Giuseppe Portella, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy. E-mail: . portella{at}unina.it

Abstract

Being one of the most lethal human neoplasms and refractory to such conventional treatment as chemo- and radiotherapy, anaplastic thyroid carcinoma is a prime target for innovative therapy. p53 gene inactivation is a constant feature of this neoplasia. Therefore, we evaluated a therapeutic approach based on an E1B 55-kDa gene-defective adenovirus (ONYX-015) that replicates only in cells with impaired p53 function and leads to cell death. Here we report that the ONYX-015 virus induces cell death in three human thyroid anaplastic carcinoma cell lines (ARO, FRO, and KAT-4). In addition, we found that the growth of xenograft tumors induced in athymic mice by the injection of ARO cells was drastically reduced by ONYX-015 treatment. The ONYX-015 virus worked synergistically with two antineoplastic drugs (doxorubicin and paclitaxel) in inducing ARO and KAT-4 cell death. These results suggest that ONYX-015 may be a valid tool in the treatment of the human thyroid anaplastic carcinoma.

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