SLT-VEGF for anti-angiogenic therapy of melanoma

SLT-VEGF 用于黑色素瘤的抗血管生成治疗

• 批准号: 6987676
• 负责人: CARL Venton HAMBY
• 金额: $ 13.42万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6987676
• 关键词: angiogenesis inhibitors; antineoplastics; apoptosis; athymic mouse; cell growth regulation; chemical conjugate; clinical research; growth factor receptors; human subject; interferon alpha; melanoma; metastasis; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; neoplasm /cancer transplantation; nonhuman therapy evaluation; shiga toxin; tissue /cell culture; vascular endothelial growth factors; vascular endothelium

DESCRIPTION (provided by applicant): The goal of this investigation is to assess the efficacy of a novel anti-angiogenic agent comprised of Shiga-like toxin A fused to vascular endothelial growth factor (SLT-VEGF) alone and in combination with another anti-angiogenic compound, IFN-alpha, in inhibiting the growth of human endothelial precursor cells in vitro and that of human melanoma tumors grown in nude mice. A pharmacological audit trail will be established in the proposed experiments to determine: 1) the presence of the SLT-VEGF target molecule, VEGF receptor-2 (KDR), on human endothelial cell colonies and in the vasculature of human melanoma tumors, 2) the degree of apoptosis induced by SLT-VEGF treatment alone and in combination with IFN-alpha, 3) the pharmacodynamic effects of SLT-VEGF alone and in combination with IFN-alpha on the IC50 of human endothelial precursor cells in vitro and 4) the biologic effects of SLT-VEGF alone and in combination with IFN-alpha on human melanoma tumor growth in vivo and on changes in serum levels of angiogenesis-related compounds. In addition the efficacy of SLT-VEGF alone and in combination with IFN-alpha in preventing metastatic disease will be assayed by treating mice whose primary melanoma tumor explants have been surgically removed. The information obtained in this study will provide a rational basis for deciding whether SLT-VEGF alone or combined with IFN-alpha will be suitable for further development and testing in clinical trials with human patients.

描述（由申请人提供）：这项研究的目的是评估由志与血管内皮生长因子（SLT-VEGF）组成的新型抗血管生成剂（SLT-VEGF）的功效裸鼠。在拟议的实验中将建立一条药理审核步道，以确定：1）在人类内皮细胞菌落上的存在SLT-VEGF靶分子VEGF受体-2（KDR）以及人类黑色素瘤肿瘤的脉管系统，2）与单独治疗的型和植入型的腹膜化程度，以及Ifn and in-vegf的程度。单独使用SLT-VEGF并与人体内皮前体细胞IC50上的IFN-Alpha结合在一起，4）单独使用SLT-VEGF的生物学作用，并结合IFN-α对人类黑色素瘤肿瘤在体内的生长以及血管生成率降低的血清中的血清肿瘤的变化。此外，仅通过治疗将原发性黑色素瘤肿瘤外植体的小鼠通过手术去除的小鼠来测定单独使用SLT-VEGF并与IFN-α在预防转移性疾病中的功效。在这项研究中获得的信息将提供合理的基础，以决定单独使用SLT-VEGF或与IFN-Alpha合并，适合于人类患者的临床试验进行进一步开发和测试。