Data from Oncolytic Herpes Simplex Virus Vector G47Δ in Combination with Androgen Ablation for the Treatment of Human Prostate Adenocarcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> The use of oncolytic herpes simplex virus type 1 is a promising stategy for cancer treatment. We constructed herpes simplex virus type 1 vector G47Δ by deleting the <i>α47</i> gene and the promoter region of <i>US11</i> from G207. We now report studies demonstrating the potential of G47Δ as a therapeutic modality for prostate cancer in combination with androgen ablation.</p><p><b>Experimental Design:</b> The cytopathic activities of G47Δ at low multiplicities of infection was tested in human prostate cancer cell lines LNCaP, PC-3, and DU145 <i>in vitro</i>. Two androgen-dependent mouse s.c. tumor models, murine TRAMP and human HONDA, were used to investigate the <i>in vivo</i> efficacy of G47Δ in combination with androgen ablation.</p><p><b>Results:</b> G47Δ at low multiplicities of infection showed more rapid tumor cell killing than G207 in LNCaP and DU145 <i>in vitro</i> and showed a 22-fold higher virus yield in a single-step growth experiment. <i>In vivo</i>, G47Δ treatment resulted in reduced tumor growth of established s.c. TRAMP and HONDA tumors and inhibited the growth of recurrent HONDA tumors that once regressed by androgen ablation therapy. In both TRAMP and HONDA tumor xenografts, the combination therapy of G47Δ with androgen ablation led to significantly enhanced inhibition of the tumor growth and prolonged survival.</p><p><b>Conclusions:</b> These results suggest that oncolytic virus therapy with G47Δ can be usefully combined with androgen ablation therapy for the treatment of prostate cancer.</p></div>