Directing Tumor-specific T cells to Tumors

将肿瘤特异性 T 细胞引导至肿瘤

• 批准号: 8518920
• 负责人: Pawel Kalinski
• 金额: $ 15.25万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-27 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8518920
• 关键词: Directing; Tumor; specific; cells; Tumors

DESCRIPTION (provided by applicant): We will evaluate the overall hypothesis that the combined treatment with the vaccines that induce particular chemokine receptors (CKR) on tumor-specific effector T cells with the treatments that induce the production of the relevant chemokines selectively within tumors, will result in therapeutic synergism, by directing tumorspecific T cells to tumors. Our proposal is based on our development of a new dendritic cell variant (aDC1s) with a unique ability of to induce a defined pattern of CKRs on tumor-specific T cells (selectively-enhanced expression of CXCR3 and CCR5), and our development of several complementary strategies to selectively enhance the production of the relevant chemokines in different tumor tissues. This Program involves three Research Projects: Project 1: Tumor-Specific Chemokine Modulation in Colorectal Cancer versus Melanoma; Project 2: Type-1 Antigen Presenting Cells in the CMS Tumors: the Key to Efficient Anti-tumor Immunity; Project 3: Tumor-selective Oncolytic Vaccinia Virus and aDC1-based Vaccine as a Combination Therapy for Colorectal Cancer. Our ongoing clinical trials in melanoma, colorectal cancer, and glioma, will provide the patient material for the laboratory studies proposed in years 1-3. The paradigms and methods developed within this period will result in the clinical introduction of new combination therapies of cancer (vaccination + chemokine-targeting regimen) that will be clinically tested in years 4-5 of this Program.

描述（由申请人提供）：我们将评估总体假设，即用诱导特定趋化因子受体（CKR）在肿瘤特异性效应T细胞上的疫苗结合治疗，并通过指导肿瘤中选择性地产生相关趋化因子的治疗方法，导致治疗性同性恋因子，通过引导性tumors tumors tumors tamors tamorsific T细胞。我们的建议基于我们开发新的树突状细胞变体（ADC1），具有在肿瘤特异性T细胞上诱导CKR的明确模式的独特能力（选择性增强的CXCR3和CCR5表达），以及我们对几种互补策略进行选择，以选择性地增强不同肿瘤组织中相关趋化性的产生。该计划涉及三个研究项目：项目1：大肠癌与黑色素瘤中肿瘤特异性趋化因子调节；项目2：CMS肿瘤中的1型抗原呈现细胞：有效抗肿瘤免疫的关键；项目3：肿瘤选择性癌性疫苗病毒和基于ADC1的疫苗作为结直肠癌的联合疗法。我们正在进行的黑色素瘤，大肠癌和神经胶质瘤的临床试验将为1 - 3年级提出的实验室研究提供患者材料。在此期间开发的范例和方法将导致临床引入癌症的新组合疗法（疫苗接种 +趋化因子靶向方案），该疗法将在该计划的4 - 5年内进行临床测试。