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博士提供一条作为研究人员获得独立的途径。Sarnaik博士的长期职业目标是成为一名成熟的翻译科学家，在外科免疫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翻译实验室研究、生物统计学和Grnt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，旨在利用莫菲特癌症中心的现有资源以及培训计划中包括的导师的具体专业知识。拟议的研究计划是Sarnaik博士初步数据的合乎逻辑的扩展。这包括实施一项I期临床试验，将共刺激抗体和过继细胞疗法与肿瘤浸润性淋巴细胞(TIL)相结合，用于治疗无法切除的IV期黑色素瘤患者。过继细胞治疗是转移性黑色素瘤免疫治疗的最新创新，与共刺激抗体相结合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。结果将直接导致第二阶段试验的发展。职业发展培训计划将包括杰弗里·韦伯博士的密切指导，以及一个咨询委员会的监督。赠款的共同导师将在第一阶段临床试验设计和分析、转化性实验室研究、临床试验开发和生物统计学方面提供额外的培训。职业发展计划的关键要素包括：每周与韦伯博士的互动、临床药理学的轮换、临床研究单位(第一阶段/第二阶段试验监测和护理)以及詹姆斯·穆尔博士的实验室。此外，还将获得李智贤博士的生物统计学培训和赠款撰写方面的培训。预计这些经验将导致在赠款期限结束时提交R01。莫菲特癌症中心为这一机会提供了理想和独特的培训环境。这项K23培训拨款中建议的培训将使Sarnaik博士能够过渡到一名独立的翻译和临床试验研究人员。

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.