Co-Stimulation to Enhance Adoptive Cell Therapy for Metastatic Melanoma

联合刺激增强转移性黑色素瘤的过继细胞疗法

• 批准号: 8565885
• 负责人: Amod Sarnaik
• 金额: $ 18.76万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8565885
• 关键词: Adoptive Cell Transfers; Adoptive Transfer; Advisory Committees; Antibodies; Beryllium; Biological Assay; Biological Markers; Biometry; Blocking Antibodies; Cancer Center; Caring; Cell Therapy; Cell physiology; Cell surface; Cellular biology; Cessation of life; Clinical; Clinical Pharmacology; Clinical Research; Clinical Trials; Clinical Trials Design; Combined Modality Therapy; Data; Development; Development Plans; Dose; Elements; Enhancing Antibodies; Environment; Exhibits; Future; Goals; Grant; Harvest; Health; Immune; Immune response; Immunotherapy; In complete remission; Infiltration; Interleukin-2; Knowledge; Laboratories; Laboratory Research; Lead; Lymphocyte; Mediating; Mentors; Metastatic Melanoma; Monitor; Outcome; Pathway interactions; Patients; Phase; Phase I Clinical Trials; Phase I/II Trial; Phase II Clinical Trials; Progression-Free Survivals; Regimen; Research; Research Personnel; Resected; Resources; Rotation; Safety; Scientist; Signal Pathway; Specimen; Staging; T-Lymphocyte; Testing; Training; Translating; Treatment Protocols; Tumor-Infiltrating Lymphocytes; Unresectable; Work; Writing; base; career; career development; chemotherapy; cohort; design; experience; improved; in vivo; innovation; melanoma; pilot trial; programs; response; skills; translational clinical trial; tumor

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.

描述（由申请人提供）：拟议的职业发展培训计划将为候选人阿莫德萨尔奈克博士提供一条独立成为研究人员的途径。Sarnaik博士的长期职业目标是成为一名成熟的转化科学家，拥有面向手术的免疫早期临床试验的专业知识。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grnt写作的特定技能。培训计划包括在每个这些元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博士初步数据的合理延伸。这包括实施I期临床试验，其将共刺激抗体和过继性细胞疗法与肿瘤浸润淋巴细胞（TIL）组合用于患有IV期黑素瘤的患者，所述IV期黑素瘤出于治愈目的不可切除。免疫细胞疗法是转移性黑色素瘤免疫疗法的最新创新，与共刺激抗体的组合具有改善患者结局的潜力。该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对T细胞介导的抗肿瘤应答重要的已知因素来确定。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。该补助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，临床药理学的轮换，临床研究单位（I/II期试验监测和护理）以及James穆尔博士的实验室。此外，将获得Ji-Hyun Lee博士的生物统计学培训和赠款撰写培训。预计这些经验将导致R 01提交的赠款期限结束。莫菲特癌症中心为这个机会提供了一个理想和独特的培训环境。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翻译和临床试验研究人员。