Enhancing Viral Oncolysis with Vasculostatin Gene Delivery

描述（由申请方提供）：本提案的最终目标是了解表达Vstat120的溶瘤病毒对OV增殖、肿瘤生物学和抗肿瘤疗效的贡献。这些结果将导致更好地理解OV治疗诱导的肿瘤生物学变化，并将导致双武装癌症杀伤OV的发展。肿瘤的OV治疗依赖于病毒的癌症特异性复制，导致肿瘤破坏，对邻近的非肿瘤组织具有最小的毒性。使用可复制OV治疗恶性胶质瘤患者的六项临床试验的结果表明，新的模式相对安全，但对疗效的高期望仍未得到满足（1，2）。肿瘤的微环境越来越被认为是其进展及其对治疗反应的重要决定因素。我的实验室最近创造了两种溶瘤病毒，带有抗血管生成基因。我们现在建议阐明这种血管生成抑制蛋白在病毒繁殖、胶质瘤生物学和OV疗效中的作用。

DESCRIPTION (provided by applicant): The ultimate goal of this proposal is to understand the contribution of Vstat120 expressing oncolytic viruses on OV propagation, tumor biology and anti-tumor efficacy. These results will lead to a better understanding of OV therapy induced changes in tumor biology and will lead to the development of a dually armed cancer killing OV. The OV treatment of tumors relies on cancer-specific replication of the virus leading to tumor destruction with minimal toxicity to adjacent non-neoplastic tissue. Results from six clinical trials using replication competent OVs to treat patients with malignant glioma have shown the new modality to be relatively safe, but high expectations of efficacy remain unmet (1, 2). The tumor's microenvironment is increasingly recognized as an important determinant for its progression and its response to therapeutics. My laboratory has recently created two oncolytic viruses, armed with an anti-angiogenic gene. We now propose to elucidate the role of this angiostatic protein in viral propagation, glioma biology and OV efficacy.