Combined Cytokine-Monoclonal Antibody Therapy - Lymphoma

细胞因子-单克隆抗体联合治疗 - 淋巴瘤

• 批准号: 6801140
• 负责人: Pierluigi Porcu
• 金额: $ 13.55万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6801140
• 关键词: B cell lymphoma; CD antigens; antineoplastics; cell mediated cytotoxicity; clinical research; clinical trial phase I; clinical trial phase II; combination chemotherapy; human subject; human therapy evaluation; interleukin 2; leukocyte activation /transformation; monoclonal antibody; natural killer cells; neoplasm /cancer chemotherapy; neoplasm /cancer immunology; patient oriented research

This application is a synthesis of didactic training in clinical research, translational immunology and clinical protocol development. Its focus is the study of cytokine-induced modulation of innate immunity in combination with monoclonal antibody (mAb) therapy as a novel immunotherapeutic approach in lymphoma. Its goals are to discover the role played by specific innate immune effector cell subsets in the anti-lymphoma activity of mAbs in vivo and to learn how in vivo modulation of effector cell subsets with cytokines, such as interleukin-2 (IL-2), might enhance the clinical effectiveness of mAbs. The applicant is an Assistant Professor of Internal Medicine at The Ohio State University (OSU) with extensive training in basic cancer laboratory research, cytokine biology, and medical oncology, with a strong concentration in lymphoma. For his academic career development, the applicant has chosen the arena of clinical research in hematological malignancies, with a specific focus in lymphoma. OSU has assembled a cadre of outstanding investigators with expertise in clinical cancer research, particularly in the area of hematological malignancies, providing an excellent environment for career development. The mentor for this application is a recognized leader in the study of the immune system and its role in the pathogenesis and therapy of lymphoma, and has an extensive track record of training successful physician-scientists. This proposal presents two specific aims: Specific Aim 1: To participate in a NIH K30- funded Clinical Research Curriculum (CRC) specifically designed for the development of clinical investigators at OSU. Specific Aim 2: Based on extensive pre-clinical observations made in the mentor's laboratory, the applicant will complete a Phase I and initiate a Phase II study of rituximab (anti-CD20 monoclonal antibody) and interleukin-2 (IL-2) in relapsed B-cell lymphoma. Correlative science studies in Specific Aim 2 will focus on the study of NK-cells, Fcgamma receptors, ADCC, and pharmacokinetics, with the goal of elucidating the interactions between the innate immune system and rituximab that are relevant to the clinical anti-lymphoma activity of rituximab. These studies will advance our knowledge about the role of the innate immune system in the therapy of lymphoma and may lead to a broader use of cytokine-mAb combinations in the therapy of cancer.

该应用程序综合了临床研究、转化免疫学和临床方案开发方面的教学培训。其重点是研究细胞因子诱导的先天免疫调节与单克隆抗体 (mAb) 疗法相结合，作为淋巴瘤的新型免疫治疗方法。其目标是发现特定先天免疫效应细胞亚群在单克隆抗体体内抗淋巴瘤活性中所发挥的作用，并了解如何用细胞因子（例如白细胞介素-2 (IL-2)、可能会增强单克隆抗体的临床效果。申请人是俄亥俄州立大学 (OSU) 的内科助理教授，在基础癌症实验室研究、细胞因子生物学和肿瘤内科（尤其是淋巴瘤）方面接受过广泛的培训。为了他的学术职业发展，申请人选择了血液恶性肿瘤的临床研究领域，特别关注淋巴瘤。俄勒冈州立大学聚集了一批在临床癌症研究，特别是血液恶性肿瘤领域具有专业知识的优秀研究人员，为职业发展提供了良好的环境。该应用程序的导师是免疫系统及其研究领域公认的领导者 在淋巴瘤的发病机制和治疗中发挥重要作用，并在培训成功的医师科学家方面拥有广泛的记录。该提案提出了两个具体目标： 具体目标 1：参加 NIH K30 资助的临床研究课程 (CRC)，该课程专为俄勒冈州立大学临床研究人员的发展而设计。具体目标2：根据导师实验室进行的广泛临床前观察，申请人将完成利妥昔单抗（抗CD20单克隆抗体）和白细胞介素2（IL-2）治疗复发性癌症的I期研究并启动II期研究B 细胞淋巴瘤。具体目标 2 中的相关科学研究将集中于 NK 细胞、Fcgamma 受体、ADCC 和药代动力学的研究，目的是阐明 先天免疫系统和利妥昔单抗之间的相互作用与利妥昔单抗的临床抗淋巴瘤活性相关。这些研究将增进我们对先天免疫系统在淋巴瘤治疗中作用的认识，并可能导致细胞因子-单克隆抗体组合在癌症治疗中更广泛的应用。