Targeted Therapy of B-cell Malignancies

B细胞恶性肿瘤的靶向治疗

• 批准号: 7478745
• 负责人: DAVID M GOLDENBERG
• 金额: $ 161.81万
• 依托单位: CTR FOR MOLECULAR MEDICINE/IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-30 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478745
• 关键词: Targeted; Therapy; cell; Malignancies

DESCRIPTION (provided by applicant): This P01 application will focus on a variety of targeted immunotherapy approaches for the treatment of B-cell malignancies, such as non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), and chronic lymphocytic lymphoma (CLL). It is comprised of 3 preclinical projects and one clinical project, which are supported by 6 cores. This program project represents a collaboration of three institutions along with additional collaborations and advice of leading experts in each of the research areas. A number of antigen targets will be examined: CD20, CD22, CD74, and HLA-DR because these appear to be the most promising from our own published studies and those of others, and because we now have access to humanized (CDR-grafted) forms of these antibodies. The overall goal is to develop immunotherapy strategies for the more effective, targeted therapy of these neoplasms with one or more of these MAbs, in one or more forms (unlabeled, radiolabeled, and/or drug conjugated), and to be used alone or in combination with other modalities. Of particular interest is the rapid translation of basic and preclinical studies to the clinic. In this regard, 2 clinical protocols, one using a combination of 90Y-humanized anti-CD22 IgG with Rituxan and another utilizing a recombinant bispecific antibody pretargeting approach are planned. However, the immediate goals of this project are to better understand how these various reagents can function alone or in certain combinations for the more effective therapy of B-cell malignancies and to gain a better understanding of the mechanisms involved in their actions, in tumor resistance, and in predicting which tumor types will respond best. Collectively, the integration of all of these different, but related endeavors promises to provide new knowledge and strategies for the improved management of B-cell malignancies.

描述（由申请人提供）：本 P01 申请将重点关注用于治疗 B 细胞恶性肿瘤的多种靶向免疫治疗方法，例如非霍奇金淋巴瘤 (NHL) 和多发性骨髓瘤 (MM) 以及慢性淋巴细胞淋巴瘤 (CLL) ）。它由3个临床前项目和1个临床项目组成，由6个核心支持。该计划项目代表了三个机构的合作以及每个研究领域领先专家的额外合作和建议。将检查许多抗原靶点：CD20、CD22、CD74 和 HLA-DR，因为从我们自己发表的研究和其他人的研究来看，这些似乎是最有前途的，而且因为我们现在可以获得人源化（CDR 移植）这些抗体的形式。总体目标是开发免疫治疗策略，使用一种或多种单克隆抗体以一种或多种形式（未标记的、放射性标记的和/或药物缀合的）对这些肿瘤进行更有效的靶向治疗，并单独使用或联合使用。与其他方式相结合。特别令人感兴趣的是基础和临床前研究快速转化为临床。在这方面，计划有 2 种临床方案，一种使用 90Y 人源化抗 CD22 IgG 与 Rituxan 的组合，另一种使用重组双特异性抗体预靶向方法。然而， 该项目的直接目标是更好地了解这些不同的试剂如何单独或以某些组合方式发挥作用，以更有效地治疗 B 细胞恶性肿瘤，并更好地了解其作用、肿瘤抵抗和治疗中涉及的机制。预测哪种肿瘤类型反应最好。总的来说，所有这些不同但相关的努力的整合有望为改善 B 细胞恶性肿瘤的治疗提供新的知识和策略。