154. Relationship between the Expression of Membrane Receptors (CAR, Integrin αvβ3 and Integrin αvβ5 ) and Adenoviral Transduction Efficiency

Abstract

Recent reports demonstrated that GM-CSF (Granulocyte Macrophage colony-Stimulating Factor)-transduced tumor vaccines (GVAX) had substantial antitumor activity in preclinical cancer models and partially in clinical situations because of their chemotactical attraction and activation of dendritic cells. To produce GVAX efficiently, recombinant type 5 E1 deleted adenovirus encoding human GM-CSF is one of the most promising vectors (AdenoGVAX). Adenoviral gene transduction is currently considered to be mediated by CAR (Coxsackie-Adenovirus Receptor), integrin|[alpha]|v|[beta]|3 and integrin|[alpha]|v|[beta]|5. Although previous reports showed that CAR and the integrin groups could alternatively be used for adenoviral transduction in limited cells, systematical data focusing on the relationship between the expression of membrane receptors (CAR, integrin |[alpha]|v|[beta]|3 and integrin |[alpha]|v|[beta]|5) and adenoviral transduction efficiency has not been reported. As high GM-CSF production is considered to be required to obtain clinical effects, prediction of GM-CSF production from AdenoGVAX transduced tumor cells is critical to perform the clinical trial efficiently. In this study, we reported the relationship between the expression of membrane receptors and adenoviral mediated GM-CSF production rate in renal cell carcinoma (RCC) cells and non small lung carcinoma (NSCLC) cells.