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Transduction of Dendritic Cells with Bcl-x_L Increases Their Resistance to Prostate Cancer-Induced Apoptosis and Antitumor Effect in Mice¹

Georgi Pirtskhalaishvili^*, Galina V. Shurin, Andrea Gambotto, Clemens Esche, Madeline Wahl, Zoya R. Yurkovetsky, Paul D. Robbins and Michael R. Shurin^2,

Departments of ^* Urology, Surgery, and Biochemistry and Molecular Genetics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells (DC), which might block the development of specific antitumor immune responses. Analysis of murine prostatic carcinoma tissues revealed the significant decrease in intratumoral DC number during tumor progression. We demonstrated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-x_L. Next, we evaluated the resistance to tumor-induced apoptosis and the antitumor efficiency of genetically engineered DC overexpressing Bcl-x_L. DC were transduced with an adenoviral vector encoding the murine Bcl-x_L gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice with Bcl-x_L-transduced DC resulted in significant inhibition of tumor growth compared with the administration of nontransduced DC. Thus, our data suggest that the protection of DC from PCa-induced apoptosis might significantly increase the efficacy of DC-based therapies in cancer even in the absence of available tumor-specific Ags.

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