Combination of Oncolytic Adenoviral Therapy with Chemotherapy for Enhanced Breast Cancer Cell Killing – Virotherapy in combination with chemotherapy

Combination of Oncolytic Adenoviral Therapy with Chemotherapy for Enhanced Breast Cancer Cell Killing

Oncolytic adenoviruses are emerging agents for treatment of cancer by tumor-restricted virus replication, cell lysis and virus spread. A promising oncolytic adenovirus agent, known as Ad5-Δ24-RGD, harbors a 24-bp deletion in the E1A gene that abrogates the binding of E1A to the retinoblastoma tumor suppressor (Rb). As with conventional therapy regimes, oncolytic virotherapy, by itself, has limited success in complete tumor eradication in both preclinical animal models and clinical studies. Combination of anticancer agents with different modes of action remains a mainstay in cancer treatment. We undertook one approach towards this end by combining oncolytic adenoviral therapy with chemotherapy. In this study, we investigated a combination treatment of breast cancer cells with Ad5-Δ24-RGD and Docetaxel. Our results indicate a synergistic effect between Docetaxel and Ad5-Δ24-RGD in breast cancer cell killing at a lower dose than either agent alone. These results suggest that viral replication was not inhibited by this chemotherapy treatment and that chemotherapy could reduce the amount of viral particles needed to help eradicate the tumor. Administration of lower viral loads would simultaneously improve safety and decrease immunogenicity of the vector. The inclusion of oncolytic adenoviruses into multimodal cancer treatment together with chemotherapy has a potential to become powerful therapeutic regimen.

virotherapy - chemotherapy - breast cancer