Universal Vectors for the Therapy of Cancer

描述：（由申请人提供）我的近期职业目标是继续我的工作， 癌症研究领域的研究主要集中在开发 癌症治疗的新药。 为了实现这一目标，我建议开发 可用于递送DNA或细胞毒性物质的通用递送系统 分子至在其表面上表达白细胞介素-2（IL-2）的肿瘤细胞， 或转铁蛋白（Tf）受体（IL-2 R或Tf-R）。 输送系统将 具有配体的抗体融合蛋白（例如，IL-2或Tf） 共价结合或具有识别生长的可变区 因子受体（例如，抗TfR）。 含有IL-1的抗体融合蛋白 2或Tf将特异于半抗原丹磺酰基（DNS），并将用于半抗原的合成。 丹磺酰化试剂的递送。 抗TfR抗体将共价融合 与抗生物素蛋白结合，并将用于递送生物素化的试剂。 到 生产和描述运载工具，我提出以下建议 具体目标：1.生产待用的重组抗体融合蛋白 作为通用运载工具; 2.评价Ab融合能力 将蛋白质或DNA递送至体外生长的细胞的蛋白质; 3.确定 抗体融合蛋白在体内的性质及其靶向的能力 并在动物模型中消除肿瘤。 我预计， 将为治疗各种重要的 恶性肿瘤。 通用载体将使治疗肿瘤更容易， 多种抗癌药物，并将促进快速评估 潜在的新治疗剂。 虽然最初的原则将是 使用IL-2 R和/或TfR作为靶标建立，未来的通用载体可以 目标 其他肿瘤相关分子。 作为一个受过训练的 医学博士/哲学博士、我在基础科学和临床科学方面都有很强的基础。 的 我将在此期间接受的培训将提高这两个 我的研究能力和英语能力 这种额外的培训是 如果我想在一个主要的研究机构担任独立的职位， 大学 加州大学洛杉矶分校提供了一个良好的，支持性的环境， 提议的研究。 有一个大的教师与专业知识，几乎每一个 纪律 优秀的研讨会系列和技术培训课程是 available. 大学致力于我的职业发展， 提供资源，而不需要任何教学或临床活动。 的 培训期间也将让我参加国家和国际 会议，既扩大了我的专业知识和我的合作者网络， 同事

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.