Directing Tumor-specific T cells to Tumors

将肿瘤特异性 T 细胞引导至肿瘤

• 批准号: 8248336
• 负责人: Pawel Kalinski
• 金额: $ 165.18万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248336
• 关键词: Antigen-Presenting Cells; CCR5 gene; CXCR3 gene; Clinical; Clinical Trials; Colorectal Cancer; Combined Modality Therapy; Dendritic Cells; Development; Glioma; Laboratory Study; Methods; Oncolytic; Patients; Pattern; Production; Regimen; Research Project Grants; T-Lymphocyte; Testing; Therapeutic; Tumor Immunity; Tumor Tissue; Vaccination; Vaccines; Vaccinia virus; Variant; base; chemokine; chemokine receptor; combination cancer therapy; melanoma; programs; synergism; tumor

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，即用在肿瘤特异性效应T细胞上诱导特定趋化因子受体（CKR）的疫苗与在肿瘤内选择性诱导相关趋化因子产生的治疗相结合，通过将肿瘤特异性 T 细胞引导至肿瘤，从而产生治疗协同作用。我们的提案基于我们开发的一种新的树突状细胞变体 (aDC1s)，该变体具有在肿瘤特异性 T 细胞上诱导确定的 CKR 模式（选择性增强 CXCR3 和 CCR5 的表达）的独特能力，以及我们开发的几种选择性增强不同肿瘤组织中相关趋化因子产生的互补策略。该计划涉及三个研究项目： 项目 1：结直肠癌与黑色素瘤中的肿瘤特异性趋化因子调节；项目2：CMS肿瘤中1型抗原呈递细胞：高效抗肿瘤免疫的关键；项目 3：肿瘤选择性溶瘤痘苗病毒和基于 aDC1 的疫苗联合治疗结直肠癌。我们正在进行的黑色素瘤、结直肠癌和神经胶质瘤临床试验将为 1-3 年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新的癌症联合疗法（疫苗+趋化因子靶向方案）的临床引入，并将在本计划的第 4-5 年进行临床测试。