Pretargeted Radioimmunotherapy With Irreversible mAb

使用不可逆单克隆抗体进行预靶向放射免疫治疗

• 批准号: 6549968
• 负责人: DAVID A GOODWIN
• 金额: $ 9.95万
• 依托单位: LEXRITE LABS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6549968
• 关键词: drug delivery systems; drug design /synthesis /production; drug metabolism; immunologic substance development /preparation; laboratory mouse; monoclonal antibody; neoplasm /cancer radioimmunotherapy; neoplasm /cancer site; polyethylene glycols

DESCRIPTION (provided by applicant): The objective of drug targeting, especially for cancer chemotherapy and radioimmunotherapy, is to enhance the effectiveness of the drug by concentrating it at the target site, and minimizing its effects in non-target sites. Lexrite's long-term goals are to create a pretargeted radiotherapy system using multivalent target binding followed by irreversible capture of a radionuclide, to achieve high tumor uptake and radiation combined with low normal tissue uptake and radiation toxicity. This combined with long residence time in the tumor and low immunogenicity, will enable repeated therapeutic doses to be given. We will use Lexrite's proprietary new Irreversible Antibody to test the feasibility of a novel 3-step pretargeting protocol using monoclonal antibody B72.3 to image cancer sites. The human LS174T nude mouse xenograft model will be used. B72.3 is a well-studied antibody that has been used clinically for imaging and experimental radioimmunotherapy in TAG-72 positive tumors such as colorectal, breast, prostate and ovarian cancer. Effective treatment of these important cancers is a major goal. In Phase II, this system will be further developed to optimize tumor uptake and reduce background in non-target organs to facilitate pretargeted radioimmunotherapy. Successful accomplishment of the 6 milestones described in this grant application and achievement of the Phase II goals, will lay the groundwork for clinical trials with the optimized pretargeting protocol. The approach described herein will lead to innovations in other areas of targeted imaging and therapy of disease.

描述（由申请人提供）：药物靶向的目的，尤其是用于癌症化疗和放射免疫疗法，是通过将其集中在目标部位来提高药物的有效性，并最大程度地减少其在非目标部位的影响。词汇的长期目标是使用多价目标结合创建一个有预先的放射疗法系统，然后是不可逆地捕获放射性核素，以实现高肿瘤的吸收和辐射，并结合了低正常的组织摄取和辐射毒性。这与肿瘤中的长时间停留时间和低免疫原性相结合，可以给予反复的治疗剂量。我们将使用词汇专有的新型不可逆抗体来测试使用单克隆抗体B72.3的新型三步有预定性方案的可行性，以对癌症部位进行图像。将使用人类LS174T裸鼠异种移植模型。 B72.3是一种良好的抗体，在TAG-72阳性肿瘤（如结直肠癌，乳腺癌，前列腺和卵巢癌）中已用于临床上用于成像和实验性放射免疫疗法。这些重要癌症的有效治疗是一个主要目标。在第二阶段，将进一步开发该系统，以优化肿瘤的吸收并减少非目标器官的背景，以促进预定的放射免疫疗法。成功地完成了本赠款应用中描述的6个里程碑和II期目标的实现，将通过优化的预定协议为临床试验奠定基础。此处描述的方法将导致在靶向成像和疾病治疗的其他领域进行创新。