Genetically Engineered Viruses for Prostate Cancer Ther

描述（申请人提供）：单纯疱疹病毒-1 （HSV-1）作为前列腺癌治疗的溶瘤和基因转移载体有许多有吸引力的特性。尽管在过去的十年中，这一领域取得了许多进展，但我们现在描述了使用模拟人类转移性前列腺癌的相关转基因前列腺癌模型来提高治疗效果的方法。我们假设，适当选择的化疗药物联合溶瘤性HSV载体将提高抗肿瘤疗效，包括全身给药后，并且这种组合将允许使用更低、毒性更小的化疗剂量。我们将探讨溶瘤性HSV静脉给药的靶向机制和抗肿瘤效果。我们将研究表达细胞因子的HSV载体的免疫机制，这些细胞因子可以协同作用，引发前列腺癌的免疫破坏。我们假设溶瘤性HSV载体通过抑制肿瘤内的血管生成来发挥其抗肿瘤作用，而适当选择的细胞因子的表达将增强这种抗血管生成作用。我们将探讨肿瘤内和静脉给药后的这些作用机制。

DESCRIPTION (provided by applicant): Herpes simplex virus-1 (HSV-1) has many attractive features for further development as an oncolytic and gene transfer vector for prostate cancer therapy. Although many advances have been made in this field in the past decade, we now describe methods to increase the efficacy of treatment using relevant transgenic prostate cancer models mimicking human metastatic prostate cancer. We hypothesize that appropriately chosen chemotherapeutic agents combined with oncolytic HSV vectors will improve anti-tumor efficacy, including after systemic delivery, and that this combination will permit the use of lower, less toxic doses of chemotherapy. We will explore the mechanisms of targeting and anti-tumor efficacy of oncolytic HSV following intravenous delivery. We will study the immune mechanisms of HSV vectors expressing cytokines that can act synergistically to elicit immune destruction of prostate cancer. We hypothesize that oncolytic HSV vectors exert some of their anti-tumor effects by inhibiting angiogenesis within the tumor and that the expression of appropriately chosen cytokines will enhance this anti-angiogenic effect. We will explore these mechanisms of action following both intra-neoplastic and intravenous administration.