Co-Stimulation to Enhance Adoptive Cell Therapy for Metastatic Melanoma

描述（由申请人提供）：拟议的职业发展培训计划将为候选人Amod Sarnaik博士提供一条通往独立研究人员的道路。Sarnaik博士的长期职业目标是成为一名成熟的转化科学家，在以手术为导向的基于免疫的早期临床试验方面拥有专业知识。Sarnaik博士的近期目标是获得临床和转化实验室研究、生物统计学和拨款写作方面的特定技能。培训计划包括这些要素的教学和实践经验，旨在充分利用莫菲特癌症中心的现有资源以及培训计划中导师的具体专业知识。拟议的研究计划是萨尔奈克博士初步数据的合理延伸。这包括一项I期临床试验的实施，该试验结合了共刺激抗体和肿瘤浸润淋巴细胞（TIL）过继细胞疗法，用于治疗无法切除的IV期黑色素瘤患者。过继细胞疗法是最近转移性黑色素瘤免疫治疗的一项创新，与共刺激抗体联合使用有可能改善患者的预后。这项试验将确定这种联合治疗的安全性和可行性。此外，共同刺激增强结果的机制将通过研究T细胞介导的抗肿瘤反应的已知重要因素来确定。结果将直接导致II期试验的开展。职业发展培训计划将由杰弗里·韦伯博士密切指导，并由一个咨询委员会监督。该基金的共同导师将提供I期临床试验设计和分析、转化实验室研究、临床试验开发和生物统计学方面的额外培训。职业发展计划的关键要素包括：每周与Weber博士的互动，临床药理学的轮转，临床研究单位（I/II期试验监测和护理），以及James Mul博士的实验室。此外，还将获得李智贤博士的生物统计学培训和基金写作培训。预计这些经验将导致在拨款期限结束时提交R01。莫菲特癌症中心为这一机会提供了理想而独特的培训环境。K23培训补助金中提出的培训将使Sarnaik博士能够过渡到独立的转化和临床试验研究员。

DESCRIPTION (provided by applicant): The proposed career development training plan will provide the candidate, Dr. Amod Sarnaik, with a pathway to independence as a researcher. Dr. Sarnaik's long term career goal is to become an established translational scientist with expertise in surgically-oriented immune-based early phase clinical trials. Dr. Sarnaik's immediate goal is to acquire specific skills in clinical and translational laboratory research, biostatistics, and grnt writing. The training plan includes didactic and practical experiences in each of these elements and is designed to capitalize on existing resources at Moffitt Cancer Center as well as the specific expertise of the mentors included in the training plan. The proposed research plan is a logical extension of Dr. Sarnaik's preliminary data. This includes implementation of a phase I clinical trial that combines co- stimulatory antibodies and adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) for patients with stage IV melanoma that are unresectable for curative intent. Adoptive cell therapy is a recent innovation in immunotherapy for metastatic melanoma, and combination with co-stimulatory antibodies has the potential to improve patient outcomes. This trial will determine the safety and feasibility of this combination treatment. Additionally, the mechanisms by which co-stimulation enhances outcomes will be determined by investigating known factors important for T cell-mediated anti-tumor responses. Results will directly lead to the development of a phase II trial. The career development training plan will involve close mentoring by Dr. Jeffrey Weber, as well as oversight by an advisory committee. The co-mentors of the grant will provide additional training in phase I clinical trial design and analysis, translational laboratory research, clinical trial development, and biostatistics. Key elements of the career development plan include: weekly interactions with Dr. Weber, rotations in Clinical Pharmacology, the Clinical Research Unit (Phase I/II trial monitoring and care), and the laboratory of Dr. James Mul�. In addition, training in biostatistics by Dr. Ji-Hyun Lee and training in grant writing will be obtained. It is anticipated that these experiences will lead to a R01 submission by the end of the term of the grant. Moffitt Cancer Center provides an ideal and unique training environment for this opportunity. The training proposed in this K23 training grant will allow Dr. Sarnaik to transition to an independent translational and clinical trial researcher.