1. ¹Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
3. ³Translational Research Laboratory, Institut Catala d'Oncologia Barcelona, Barcelona, Spain

Correspondence: Dr J Fueyo, Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Box 1002, 1515 Holcombe Blvd, Houston, TX 77030, USA. E-mail: jfueyo@mdanderson.org

Received 17 January 2007; Revised 20 April 2007; Accepted 8 May 2007; Published online 8 June 2007.

Abstract

Novel therapies are clearly needed for gliomas, and the combination of oncolytic vectors with chemotherapy possesses a significant hope for the treatment of this malignancy. In addition, combination with chemotherapy allows for lower virus doses to achieve anticancer effect, thus resulting in lower undesirable toxicities due to viral proteins. In this work, we sought to determine whether combination of an oncolytic adenovirus ICOVIR-5, with RAD001 or temozolomide (TMZ) could result in enhanced anti-glioma effect in vivo. We assessed the in vitro cytotoxic effect and replication properties of ICOVIR-5 in combination with RAD001 or TMZ in U87 MG glioma cell line by MTT and TCID₅₀, respectively. Our data showed that in vitro treatment with RAD001 or TMZ not only interfered with adenovirus replication but, in addition, enhanced its oncolytic properties. To evaluate the in vivo anticancer effect, athymic mice bearing glioma xenografts (5 10⁵ U87 MG cells/animal) received a single intratumoral injection of ICOVIR-5 (10⁷ PFU/animal). RAD001 was given as a regimen of 5 mg/kg 5 days per week until the end of the experiment and TMZ was administered for 5 days at 7.5 mg/kg/mice. Of significance, combination of ICOVIR-5 with RAD001 or TMZ showed a potent anti-glioma effect in vivo, resulting in a dramatic extension of the median animal survival and in 20–40% animals becoming free of disease beyond 90 days.