CpG ODN as an Immune Adjuvant

CpG ODN 作为免疫佐剂

• 批准号: 6797383
• 负责人: GEORGE J. WEINER
• 金额: $ 29.54万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-10 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6797383
• 关键词: B cell lymphoma; B lymphocyte; CpG islands; blood chemistry; cell mediated cytotoxicity; chronic lymphocytic leukemia; clinical research; clinical trials; colony stimulating factor; combination cancer therapy; cytokine; drug interactions; drug screening /evaluation; genetically modified animals; human subject; human therapy evaluation; immunocytochemistry; immunofluorescence technique; immunomodulators; interleukin 2; laboratory mouse; monoclonal antibody; neoplasm /cancer immunotherapy; nonhuman therapy evaluation; outcomes research

DESCRIPTION (provided by applicant): Monoclonal antibodies (moAbs) are now an accepted component of therapy for the B-cell malignancies, however there is still much that we do not understand about their mechanism of action. Factors related to both the target cell and effector mechanisms appear to play important roles. There is growing evidence that combining moAb with other agents can enhance the efficacy of therapy. One such class of agents, known as immunostimulatory CpG oligodeoxynucleotides (CpG ODN), may be particularly effective due to their ability to induce coordinated production of a variety of cytokines that can enhance ADCC. CpG ODN also has effects on malignant B cells that could render them more sensitive to moAb therapy. The overall hypothesis of the current proposal is that CpG ODN, either alone or combined with other immunostimulatory agents, have effects on both malignant B cells and immune effector cells that will enhance the efficacy of anti-B cell moAb therapy. Three Specific Aims are proposed to pursue this hypothesis. Aim one will utilize murine models to determine whether agents that activate different effector cell populations, including CpG ODN of the A and B classes, IL2 and GM-CSF, are synergistic in their ability to enhance the efficacy of moAb therapy. Aim 2 will explore whether vitro therapy of Chronic Lymphocytic Leukemia (CLL) cells with CpG ODN alters the phenotype and function of the CLL cells and immune effector cells in a manner that would be expected to enhance the efficacy of moAb therapy. Aim 3 will assess whether clinical CpG ODN therapy of patients with CLL in a pilot trial is able to induce phenotypic and functional changes on the CLL cells, immune effector cells, and cytokines in a manner that would be expected to enhance the efficacy of moAb therapy. The results of these studies will allow for the rational design of the next generation of moAb-based approaches to the therapy of B-cell and other malignancies.

描述（由申请人提供）：单克隆抗体（MOABS）现在已成为B细胞恶性肿瘤治疗的公认组成部分，但是我们仍然对它们的作用机理不了解。与目标细胞和效应子机制相关的因素似乎起着重要作用。越来越多的证据表明，将MOAB与其他药物相结合可以增强治疗的功效。一种这样类型的药物，称为免疫刺激性CpG寡脱氧核苷酸（CPG ODN），由于它们能够诱导各种可以增强ADCC的细胞因子的协调产生，因此可能特别有效。 CPG ODN还对恶性B细胞具有影响，使它们对摩押治疗更敏感。当前建议的总体假设是，单独或与其他免疫刺激剂相结合的CpG ODN对恶性B细胞和免疫效应细胞都有影响，从而增强了抗B细胞摩映治疗的功效。提出了三个具体目标来提出这一假设。 AIM ONE将利用鼠模型来确定激活不同效应细胞群体（包括A和B类的CpG ODN）的药物IL2和GM-CSF是否具有增强摩押治疗功效的能力。 AIM 2将探索具有CpG ODN的慢性淋巴细胞性白血病（CLL）细胞的体外治疗是否会以预期增强MOAB疗法有效性的方式改变CLL细胞和免疫效应细胞的功能。 AIM 3将评估在试验试验中，CLL患者对CLL患者的临床CPG ODN治疗是否能够以一种预期的方式诱导CLL细胞，免疫效应细胞和细胞因子对CLL细胞，免疫效应细胞和细胞因子的临床型变化。这些研究的结果将允许下一代基于MoAb的B细胞和其他恶性肿瘤的方法的合理设计。