MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW

指导患者导向的研究职业发展 AW

• 批准号: 6792141
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792141
• 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.

(改编自申请人的摘要)：克隆的使用 作为细胞毒中介分子效应器和载体的抗体构建物 随着分子生物学的进步改善了 调查人员对重要的变化的理解 肿瘤发生学。同样，细胞表面分子的选择和研究进展 药物输送增加了从中受益的可能性 抗肿瘤方法。拟议的研究将利用不同的 通过抗体选择性传递优先靶点的策略 恶性细胞。这些研究的具体目的是：1)探索 使用单抗作为血管生成的抑制剂；2)探索其用途 作为一种抗肿瘤策略的靶向递送毒素；以及3)探索 抗体导向的超抗原选择性肿瘤递送增强宿主 对肿瘤的反应。第一项研究将评估阿司匹林的药代动力学 人源化抗体，并评价其在肿瘤部位的定位能力。这个 该抗体的唯一靶点是肿瘤诱导的新生血管。在一个 第二次计划的试验，波西博士将评估安全性，时间表 抗体的给药、免疫应答和初步活性 片段选择性地将一种有效的细菌毒素输送到肿瘤组织。这个 第三个试验涉及使用化学上与 不治之症乳腺癌患者的超抗原。最佳剂量， 免疫反应和抗肿瘤反应将被确定。波西博士会 在主任阿尔伯特·F·洛布利奥博士的指导下进行这些试验 亚利桑那大学综合癌症中心。 尽管最近取得了进展，但仍有许多悬而未决的问题 将需要结合临床研究和基础科学来发展 有效的抗肿瘤治疗。重新燃起了对工业界和 重组技术的进步，新的有希望的药物正在涌现 需要熟练的调查人员进行开发。这一奖品将是 波西博士成为一名熟练的独立调查员的关键 有能力竞争未来的支持。

项目成果

A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors.

• 发表时间: 2002-10
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: J. Posey;M. Khazaeli;M. Bookman;A. Nowrouzi;W. Grizzle;J. Thornton;D. Carey;J. Lorenz;A. Sing;C. Siegall;A. Lobuglio;M. Saleh

A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma.

• 发表时间: 2003-04
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: J. Posey;T. Ng;Baolian Yang;M. Khazaeli;M. Carpenter;F. Fox;M. Needle;H. Waksal;A. Lobuglio