A Phase 1 Study/DNA-Based Vaccine vs Prostatic Acid Pase

描述(申请人提供)：McNeel博士将从事以患者为导向的转化研究，重点是前列腺癌患者的免疫治疗。该提案的目标是描述职业培训和指导计划，通过该计划，他将接受适当进行人类受试者研究的培训，以及导致为前列腺癌患者进行人类疫苗试验的转化性研究计划。作为其职业发展计划的一部分，McNeel博士将完成华盛顿大学临床研究员预备课程(CIPP)。该计划是一个个性化的项目，提供生物统计学和临床研究设计、临床研究伦理、领导和管理技能、演示和教学技能、科学写作技能以及特定研究领域的专业知识等领域的教学和指导培训。此外，他还将直接接受DNA Vaccien临床试验研究领域的领军人物Mark Albertini博士的指导。CIPP执行委员会以及麦克尼尔博士在威斯康星大学的教师指导委员会(由Albertini博士、Sondel博士、Bryan博士和Bailey博士组成)将每季度跟踪他在学术和职业方面的进步。该提案的另一部分描述了一项为期5年的转化性研究计划，McNeel博士在该计划中提出了三个目标：1)在炎症性前列腺癌的大鼠模型中确定前列腺组织破坏的免疫介质；2)确定慢性炎症性前列腺癌患者中免疫识别的蛋白质；3)在人类临床疫苗试验中确定DNA疫苗在晚期前列腺癌患者中的安全性和免疫有效性。这项临床试验将针对相同的抗原，前列腺酸性磷酸酶，并使用相同的DNA免疫技术，用于在啮齿动物模型中诱导前列腺癌。这项试验将作为对提案第二个目标中确定的抗原进行临床试验评估的平台和模式。

DESCRIPTION (provided by applicant): Dr. McNeel will develop a career in patient-oriented translational research with an emphasis on the immunological treatment of patients with prostate cancer. The goal of this proposal is describe both a career training and mentoring plan through which he will receive training in the proper conduct of human subjects research, as well as a translational research plan leading to the conduct of a human vaccine trial for patients with prostate cancer. As part of his career development plan, Dr. McNeel will complete the UW Clinical Investigator Preparatory Pathway (CIPP). This program is an individualized program proviiding didactic and mentored training in the areas of biostatistics and clinical study design, clinical research ethics, leadership and management skills, presentation and teaching skills, scientific writing skills, and expertise within a specific research domain. In addition, he will be mentored directly by Dr. Mark Albertini, a leader in the field of DNA vaccien clinical trials research. His academic and career progress will be followed quarterly by the CIPP Executive Committee as well as Dr. McNeel's faculty mentoring committee at the University of Wisconsin (composed of Drs. Albertini, Sondel, Bryan and Bailey). The other part of this proposal describes a 5-year translational research plan in which Dr. McNeel proposes three aims: 1) to identify the immunological mediators of prostate tissue destruction in a rat model fo inflammatory prostatistics; 2) to identify proteins immunologically recognized in patients with chronic inflammatory prostatis; and 3) to determine in a human clinical vaccine trial the safety and immunological efficacy of a DNA-based vaccine in patients with advanced stage prostate cancer. This clinical trial will target the same antigen, prostatic acid phosphatase, and using the same DNA immunization techniques used to elicit prostatis in the rodent model. This trial will serve as a platform and model for clinical trial evaluation of antigens identified in the second aim of the proposal.