Universal Vectors for the Therapy of Cancer

描述：(申请人提供)我目前的职业目标是继续我的职业生涯 癌症研究领域的研究主要集中在发展中 癌症治疗的新药。为了实现这一目标，我建议开发 可用于传递DNA或细胞毒性的通用传递系统 肿瘤细胞表面表达白介素2的分子 转铁蛋白(Tf)受体(IL-2R或Tf-R)。交付系统将是 具有配体(例如，IL-2或Tf)的抗体融合蛋白 共价关联的或具有识别生长的可变区的 因子受体(如抗TFR)。含有IL-2的抗体融合蛋白 2或Tf将特定于半抗原dansyl(DNS)，并将用于 丹尼卡毒剂的运送。抗转铁蛋白受体抗体将被共价融合 亲和素，并将用于生物素化试剂的输送。至 制造和描述运输工具我建议如下 具体目的：1.制备待用重组抗体融合蛋白 作为通用递送载体；2.评估抗体融合的能力 向体外生长的细胞运送蛋白质或DNA的蛋白质；3.确定 抗体融合蛋白的体内性质及其靶向性研究 并在动物模型中消除肿瘤。我预计向量系统 将提供强大的工具来治疗各种重要的 恶性肿瘤。通用载体将使治疗肿瘤变得更容易 多种抗癌药物，并将有助于快速评估 潜在的新治疗药物。尽管最初的原则将是 使用IL-2R和/或TFR作为靶点建立的未来通用载体可以 靶向其他肿瘤相关分子。接受过培训，成为一名 作为医学博士，我在基础科学和临床科学方面都有很好的基础。这个 在这笔赠款期间，我将接受的培训将增强 我的研究技能和我的英语能力。这项额外的培训是 如果我要担任一个独立的职位，在一个专业从事研究，那么我就有必要 上大学。加州大学洛杉矶分校提供了一个极好的、支持的环境 拟开展的研究。有一大批教职员工，他们几乎在每一个领域都有专业知识 纪律。优秀的研讨会系列和技术培训课程是 可用。大学致力于我的职业发展，并将 提供资源，不需要任何教学或临床活动。这个 训练期还将允许我参加国内和国际比赛。 会议，既扩大了我的专业知识和我的合作者网络，又 同事们。

DESCRIPTION: (provided by Applicant) My immediate career goal is continue my research in the fields of cancer research focusing mainly in the development of new drugs for cancer therapy. To achieve this goal I propose to develop universal delivery systems that can be used to deliver DNA or cytotoxic molecules to tumor cells expressing on their surface the interleukin-2 (IL-2) or transferrin (Tf) receptor (IL-2R or Tf-R). The delivery system will be antibody fusion proteins that either have the ligand (e.g., IL-2 or Tf) covalently associated or have a variable region that recognizes a growth factor receptor (e.g., anti-TfR). The antibody fusion proteins containing IL- 2 or Tf will be specific for the hapten dansyl (DNS) and will be used for the delivery of dansylated agents. The anti-TfR antibody will be covalently fused to avidin and will be used for the delivery of biotinylated agents. To produce and characterize the delivery vehicles I propose the following specific aims: 1. Produce the recombinant antibody fusion proteins to be used as universal delivery vehicles; 2. Evaluate the ability of the Ab fusion proteins to deliver proteins or DNA to cells growing in vitro; 3. Determine the properties of the Ab fusion proteins in vivo and their ability to target and eliminate tumors in animal models. I anticipate that the vector systems will provide powerful tools for treating a wide variety of important malignancies. The universal vectors will make it easier to treat tumors with multiple anti-cancer agents and will facilitate the rapid evaluation of potential new therapeutic agents. Although initial principles will be established using IL-2R and/or TfR as targets, future universal vectors can target other tumor associated molecules. Having been trained as an M.D./Ph.D., I have a strong grounding in both basic and clinical science. The training that I will receive during the time of this grant will enhance both my research skills and my facility with English. This additional training is necessary if I am to assume an independent position doing research at a major university. UCLA provides an excellent, supportive environment for the proposed research. There is a large faculty with expertise in virtually every discipline. Excellent seminar series and technical training sessions are available. The University is committed to my career development and will provide resources without requiring any teaching or clinical activities. The training period will also allow me to attend national and international meetings, both expanding my expertise and my network of collaborators and colleagues.