MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW

指导患者导向的研究职业发展 AW

• 批准号: 6617878
• 负责人: James A Posey
• 金额: $ 12.67万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-26 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617878
• 关键词: angiogenesis inhibitors; antineoplastics; bacterial toxins; breast neoplasms; clinical research; clinical trial phase I; dosage; drug delivery systems; drug screening /evaluation; human subject; human therapy evaluation; metastasis; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplastic cell; pharmacokinetics; vitronectin

(Adapted from the applicant's abstract): The use of monoclonal antibody constructs as effectors and vectors of cytotoxic-mediating molecules are regaining attention as progress in molecular biology improves the investigators' understanding of alterations that are important in tumorigenesis. Similarly, advances in selection of cell surface molecules and drug delivery have enhanced the likelihood of deriving benefit from this antineoplastic approach. The proposed studies will make use of different strategies for selective delivery via antibody to preferentially target malignant cells. The specific aims of these studies are to: 1) explore the use of monoclonal antibodies as inhibitors of angiogenesis; 2) explore the use of targeted delivery of toxins as an anti-tumor strategy; and 3) explore selective tumor delivery of antibody-directed superantigen to enhance host response to tumors. The first study will assess the pharmacokinetics of a humanized antibody and evaluate its ability to localize at tumor sites. The unique target for this antibody is tumor induced neovascularization. In a second planned trial, Dr. Posey will evaluate the safety, schedule of administration, immune response, and preliminary activity of an antibody fragment to selectively deliver a potent bacterial toxin to tumor tissue. The third trial involves the use of an antibody fragment chemically linked to a superantigen in patients with incurable breast cancer. The optimum dose, immune response, and anti-tumor response will be determined. Dr. Posey will conduct these trials under the mentorship of Dr. Albert F. LoBuglio, Director of UAB's Comprehensive Cancer Center. Despite recent advances, there are still numerous unanswered questions that will require combining clinical research efforts and basic science to develop effective anti-noeplastic therapy. With renewed enthusiasm in industry and advances in recombinant technology, new promising agents are emerging that require development by skilled investigators. This grant award will be pivotal to Dr. Posey's progress on becoming a skilled independent investigator capable of competing for future support.

（改编自申请人摘要）：单克隆的使用 作为细胞毒性介导分子的效应物和载体的抗体构建体 随着分子生物学的进步， 研究人员对重要的改变的理解， 肿瘤发生 同样，在选择细胞表面分子和 药物输送增加了从中获益的可能性， 快速接近。 拟议的研究将利用不同的 通过抗体选择性递送以优先靶向 恶性细胞 这些研究的具体目的是：1）探索 使用单克隆抗体作为血管生成抑制剂; 2）探索使用 作为抗肿瘤策略的毒素靶向递送;以及3）探索 抗体导向的超抗原的选择性肿瘤递送以增强宿主 对肿瘤的反应。 第一项研究将评估 在一些实施方案中，本发明提供了用于检测人源化抗体并评估其在肿瘤部位定位的能力的方法。 的 该抗体的独特靶点是肿瘤诱导的新血管形成。 中 第二次计划试验，波西博士将评估安全性，时间表， 抗体的施用、免疫应答和初步活性 片段以选择性地将有效的细菌毒素递送到肿瘤组织。 的 第三个试验涉及使用化学连接到 无法治愈的乳腺癌患者的超抗原。 最佳剂量， 免疫应答和抗肿瘤应答。 波西博士会 在Albert F.博士的指导下进行这些试验。LoBuglio，主任 UAB的综合癌症中心。 尽管最近取得了进展，但仍有许多未解之谜， 将需要结合临床研究和基础科学， 有效的抗肿瘤治疗。 随着工业界重新燃起的热情， 随着重组技术的进步，新的有希望的试剂正在出现， 需要熟练的研究人员进行开发。 该奖项将在 波西博士成为一名熟练的独立调查员的关键 有能力争取未来的支持。