REGULATION OF ANTI-TUMOR IMMUNITY

抗肿瘤免疫的调节

• 批准号: 7683414
• 负责人: ECKHARD R PODACK
• 金额: $ 6.02万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-20 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683414
• 关键词: Adoptive Transfer; Antigens; Autologous Bone Marrow Transplantation; B-Lymphocytes; Biological Assay; Bone Marrow Transplantation; Cancer Vaccines; Cells; Clinical; Condition; Generations; Goals; Heat shock proteins; Hematology; Immune Tolerance; Immune response; Immunity; Immunology; Immunotherapy; Laboratories; Maintenance; Measures; Medicine; Memory; Microbiology; Modeling; Molecular; Mus; Natural Killer Cells; Non-Small-Cell Lung Carcinoma; Pathology; Pathway interactions; Patient Care; Patients; Phase I Clinical Trials; Range; Regulation; Research Personnel; Role; Testing; Time; Tumor Immunity; Vaccines; Work; base; chemokine; immunogenic; memory retention; neoplastic cell; oncology; programs; research study; response; tumor

The Program on "Regulation of Tumor Immunity" brings together investigators from the Department of Microbiology and Immunology, the Division of Hematology and Oncology in the Department of Medicine and the Department of Pathology to work together on the pressing problem of bringing Immunotherapy to a point where it can make an important contribution to patient care and treatment. The long-range goal of the program is to find ways to treat tumors with the aid of immunotherapy in the form of anti tumor vaccines. In order to develop successful immunotherapy it is necessary to define the parameters that allow the generation of anti tumor immunity and allow the maintenance of anti tumor effector functions over prolonged periods of time. Maintaining anti tumor effector responses over time necessitates our understanding of memory formation and maintenance. One important goal of the program in several projects is the elucidation of molecular mechanisms able to generate and maintain memory in the presence of established tumors. Anti tumor immunity requires TH1 polarization of the immune response. To the extent that TH2 and TH1 polarization are mutually antagonistic we suggest that elimination of TH2 responses may be beneficial for anti tumor therapy. B cells are the final effectors of TH2 polarization and we have shown that their elimination allows increased anti tumor activity. A second goal of the program examined in several projects therefore is the analysis of the mechanisms of anti tumor immunity in the absence of B cells. These studies are also aimed at the discovery of molecular pathways by which B cells dampen the anti tumor TH1 response. Our own studies and those by others support the hypothesis that the activation of the innate immune response is important for the generation of a powerful adaptive response and the generation of memory. The third goal of the program pursued therefore is the analysis of the contribution of NK cells and DC to anti tumor immunity. Since we have shown that heat shock proteins secreted by tumor cells activate DC, NK and CDS CTL this mode of activation will be studied in all projects and examined with regard to memory formation, generation of immunity in autologous bone marrow transplantation and in its effects under conditions of B cell depletion. Finally, a heat shock protein based vaccine will be used to test the hypothesis that non-immunogenic tumors are the best targets for vaccine-based immunotherapy. A phase I trial for non-small cell lung carcinoma patients will examine generation of an immune response and clinical benefit.

有关“调节肿瘤免疫”计划的计划汇集了部门的调查人员 微生物学和免疫学，医学系血液学和肿瘤学的科 病理学系在将免疫疗法带到某个地步的紧迫问题上 它可以为患者护理和治疗做出重要贡献。远程目标 计划是在抗肿瘤疫苗的形式下找到借助免疫疗法治疗肿瘤的方法。在 为了开发成功的免疫疗法，有必要定义允许的参数 产生抗肿瘤免疫力，并允许在长时间内维持抗肿瘤效应器的功能 一段时间。随着时间的流逝，保持抗肿瘤效应子的反应需要我们对 记忆形成和维护。该计划在几个项目中的一个重要目标是阐明 能够在既定肿瘤存在下产生和维持记忆力的分子机制。反对 肿瘤免疫需要Th1免疫反应的极化。在TH2和TH1的范围内 极化是相互拮抗的，我们建议消除Th2反应可能对 抗肿瘤疗法。 B细胞是Th2极化的最终效应子，我们已经表明它们 消除可以增加抗肿瘤活性。该计划在几个项目中检查的第二个目标 因此，是在没有B细胞的情况下对抗肿瘤免疫机制的分析。这些研究 还针对发现B细胞抑制抗肿瘤TH1的分子途径 回复。我们自己的研究和其他人支持先天的激活的假设 免疫反应对于产生强大的适应性反应和产生很重要 记忆。因此，该计划的第三个目标是分析NK细胞和 直流抗肿瘤免疫。由于我们已经证明肿瘤细胞分泌的热激蛋白激活 DC，NK和CDS CTL将在所有项目中研究这种激活方式，并检查 记忆形成，自体骨髓移植中的免疫力及其作用 在B细胞耗竭的条件下。最后，将使用基于热激蛋白的疫苗来测试 假设非免疫原性肿瘤是基于疫苗的免疫疗法的最佳靶标。第一阶段 非小细胞肺癌患者的试验将检查免疫反应和临床的产生 益处。