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SLT-VEGF for anti-angiogenic therapy of melanoma

SLT-VEGF 用于黑色素瘤的抗血管生成治疗

基本信息

批准号：
7140106
负责人：
CARL Venton HAMBY
金额：
$ 13.1万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2008-06-30
项目状态：
已结题

项目摘要

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）：本研究的目的是评估由志贺样毒素 A 与血管内皮生长因子 (SLT-VEGF) 融合组成的新型抗血管生成剂（单独与另一种抗血管生成化合物 IFN-α 组合）在体外抑制人内皮前体细胞生长以及在体外生长的人黑色素瘤肿瘤的功效。裸鼠。在拟议的实验中将建立药理学审计追踪，以确定：1）人内皮细胞集落和人黑色素瘤肿瘤脉管系统中是否存在 SLT-VEGF 靶分子 VEGF 受体 2（KDR），2）SLT-VEGF 单独治疗和与 IFN-α 联合治疗诱导的细胞凋亡程度，3）SLT-VEGF 的药效学作用单独的SLT-VEGF和与IFN-α组合对人内皮前体细胞体外IC50的影响，以及4)单独的SLT-VEGF和与IFN-α组合对体内人黑色素瘤肿瘤生长和血管生成相关化合物的血清水平变化的生物效应。此外，将通过治疗原发性黑色素瘤肿瘤外植体已被手术切除的小鼠来测定单独的SLT-VEGF以及与IFN-α组合在预防转移性疾病中的功效。本研究中获得的信息将为决定SLT-VEGF单独使用还是与IFN-α联合使用是否适合进一步开发和在人类患者的临床试验中进行测试提供合理的基础。