Combination of oncolytic adenoviral therapy with chemotherapy for enhanced breast cancer cell killing

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 2129
• Main Authors: Stoff-Khalili, MA, Nedeljkovic-Kurepa, A, Jung, JS, Glover, BV, Wappenschmidt, B, Rhiem, K, Bosse, K, Mallmann, P, Curiel, DT, Schmutzler, RK, Mathis, MJ
• Format: Journal Article
• Language: English
• Published: 15.01.2009
• DOI: 10.1158/0008-5472.SABCS-2129
• ISSN: 0008-5472

Abstract Abstract #2129 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 Ad5-24-RGD, harbors a 24-bp deletion in the E1A gene that abrogates the binding of E1A to the retinoblastoma tumor suppressor (Rb) and presents enhanced infectivity of primary cancer cells due to insertion of an Arg-Gly-Asp (RGD) motif into the fiber knob. Thus, Ad5-24-RGD has improved cancer cell infection efficiency due to expanded tropism toward alpha-v integrins. It also replicates selectively in cancer cells with Rb/p16 mutations. 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 Ad5-4-RGD and Docetaxel, a microtubule-stabilizing taxane that is being used in the clinic for the treatment of breast and prostate cancers and small cell carcinoma of the lung. Our results indicate a synergistic effect between Docetaxel and Ad5-24-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. Likewise lower doses of chemotherapy agents would decrease toxicity and side effects. The inclusion of oncolytic adenoviruses into multimodal cancer treatment together with chemotherapy has a potential to become powerful therapeutic regimen. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2129.