Imaging T-cell Activation and Co-stimulation in Prostate Cancer Immunotherapy

前列腺癌免疫治疗中 T 细胞激活和共刺激的成像

基本信息

批准号：
8163909
负责人：
Vladimir Ponomarev
金额：
$ 37.29万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8163909
关键词：
Animal Model Antibody Therapy Antigen Receptors Antigens Beryllium Bioluminescence Cancer Model Cancer Patient Cell Differentiation process Cell Survival Cell Therapy Cells Clinical Clinical Trials Collaborations Effectiveness Engineering Enhancers Ensure Genetic Glutamate Carboxypeptidase II Goals Human Image Imaging Techniques Imaging technology Immune response Immunotherapy Interleukin-12 Interleukin-15 Interleukin-7 Knowledge Label Laboratories Lead Ligands Link Lymphocyte Malignant Neoplasms Malignant neoplasm of prostate Mediating Methods Modality Monitor Nuclear Optical reporter Pathway interactions Patient Monitoring Patients Positron-Emission Tomography Prostate Prostate carcinoma Reporter Reporter Genes Reporting Repression Research Research Technics Resources Role STAT4 gene STAT5A gene Signal Pathway Signal Transduction Site System T-Cell Activation T-Cell Proliferation T-Lymphocyte Technology Testing Therapeutic Therapeutic Uses Time Transcriptional Activation Translating Treatment Efficacy Treatment outcome Tumor Tissue Visual Work base cancer immunotherapy clinical application cytokine human glutamate carboxypeptidase II in vivo innovation non-invasive monitor non-invasive system novel nuclear factors of activated T-cells optical imaging pre-clinical promoter response time use tool trafficking tumor

项目摘要

DESCRIPTION (provided by applicant): The objective of this application is to monitor the activation and co-stimulation of genetically altered human T-lymphocytes containing chimeric antigen receptors (CARs). T-cells can be genetically engineered to ensure their therapeutic efficacy, and to express markers that can be tracked by non-invasive imaging. Genetic labeling of lymphocytes with nuclear or optical reporter genes allows for non-invasive imaging of T-cell fate in both pre-clinical cancer models and in patients with cancer. This proposal focuses on prostate cancer, based on the genetic targeting of prostate-specific membrane antigen (PSMA). The objectives we are pursuing will increase our knowledge about the dynamics of T-cell activation, co-stimulation and duration of anti-tumor response in vivo. Specifically, using reporter gene imaging in vivo we will explore the role of selected pro- survival/proliferation co-stimulatory pathways which augment the therapeutic potency of genetically targeted T-cells. We hypothesize that genetic labeling of T lymphocytes with novel pathway-specific reporter constructs will allow for repetitive non-invasive monitoring of activation and co-stimulation in T-cells and provide an early assessment of treatment outcome during PSMA-specific adoptive T-cell immunotherapy. The role of imaging will be essential in gaining a better understanding of the duration and magnitude of T-cell activation, persistence and T-cell proliferation. The combined use of therapeutic CARs and imaging reporter genes will provide an innovative research technique and a powerful novel clinical tool in cancer immunotherapy.

描述（由申请人提供）：本应用的目的是监测含有嵌合抗原受体（CAR）的遗传改变的人类T淋巴细胞的激活和共刺激。可以在基因上进行T细胞，以确保其治疗功效，并表达可以通过非侵入性成像跟踪的标记。用核或光学报告基因对淋巴细胞的遗传标记允许在临床前癌症模型和癌症患者中对T细胞命运的无创成像。该提案的重点是前列腺癌，基于前列腺特异性膜抗原（PSMA）的遗传靶向。我们追求的目标将增加我们对体内抗肿瘤反应的T细胞激活，共刺激和持续时间的动态的了解。具体而言，使用报告基因成像在体内，我们将探讨选定的促生存/增殖共刺激途径的作用，从而增强了基因靶向T细胞的治疗效力。我们假设具有新型途径特异性报告基因构建体的T淋巴细胞的遗传标记将允许对T细胞中的激活和共刺激的重复性非侵入性监测，并在PSMA特异性的产物T细胞免疫中对治疗结果进行早期评估。成像的作用对于更好地了解T细胞激活，持久性和T细胞增殖的持续时间和幅度至关重要。治疗汽车和成像报告基因的联合使用将提供创新的研究技术和强大的癌症免疫疗法新型临床工具。