PhaseI/II Clinical Trial of hHB22.7 anti-CD22 Monoclonal Antibody for Lymphoma

hHB22.7抗CD22单克隆抗体治疗淋巴瘤I/II期临床试验

• 批准号: 7158852
• 负责人: ROBERT T O'DONNELL
• 金额: $ 26.64万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-17 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158852
• 关键词: antibody; antineoplastics; clinical research; clinical trials; immunotherapy; lymphoma; monoclonal antibody; pharmacokinetics; receptor

DESCRIPTION (provided by applicant): This Phase l/ll clinical trial employs the unique, new, anti-CD22 monoclonal antibody (mAb), humanized- HB22.7 (hHB22.7). The development of hHB22.7 was supported by the NCI's RAID program because of the antibody's ability to target a specific epitope on CD22 that leads to apoptosis in non-Hodgkin's lymphoma (NHL) cells. HHB22.7 has great potential to become a new therapy for patients with NHL. Our approach to developing anti-NHL mAbs is to examine therapeutic targets by focusing on fundamental aspects of the signaling pathways activated by engagement of lineage-specific cell surface receptors. The rationale is that identifying the ultimate physiologic consequences of receptor engagement sets the stage for receptor manipulation and development of novel, effective drugs. The excellent pre-clinical results using mHB22.7 motivated us to proceed with a clinical trial of hHB22.7. Humanized HB22.7 will allow recruitment of immune functions such as antibody and complement dependent cytotoxicity. After targeting its distinct CD22 epitope, hHB22.7 will stimulate apoptotic pathways making it a multifunctional agent against NHL. The safety, toxicity, and pharmacokinetics of 125, 250, 500 or 1000 mg/m2 of the hHB22.7 anti-CD22 mAb will be evaluated in cohorts of follicular NHL patients. Patients will receive 4 doses of hHB22.7. This study will generate the first clinical data for hHB22.7. Initial efficacy data for immunotherapy with hHB22.7 will be obtained and the dose of hHB22.7 to use in future studies will be determined. This Phase l/ll clinical study will pave the way for future clinical studies and development of hHB22.7. Lay Language Statement: Lymphoma is the sixth most common cause of cancer-related death in the United States, and one of the few malignancies that is increasing in frequency. New therapies are needed to combat this disease. HHB22.7 is an antibody that can specifically target lymphoma. We have shown that hHB22.7 can kill lymphoma cells in studies using mice, and have determined how hHB22.7 works. Antibody therapy has the potential for efficacy without much toxicity because the antibody specifically targets lymphoma. This clinical study is designed to see if hHB22.7 is safe, and promising enough to proceed to additional clinical trials.

描述（由申请人提供）：本 I/II 期临床试验采用独特的新型抗 CD22 单克隆抗体 (mAb)、人源化 HB22.7 (hHB22.7)。 hHB22.7 的开发得到了 NCI RAID 计划的支持，因为该抗体能够靶向 CD22 上的特定表位，从而导致非霍奇金淋巴瘤 (NHL) 细胞凋亡。 HHB22.7具有成为NHL患者新疗法的巨大潜力。我们开发抗 NHL mAb 的方法是通过关注谱系特异性细胞表面受体激活的信号通路的基本方面来检查治疗靶点。其基本原理是，确定受体参与的最终生理后果为受体操纵和新型有效药物的开发奠定了基础。 mHB22.7 出色的临床前结果促使我们继续进行 hHB22.7 的临床试验。人源化 HB22.7 将允许招募免疫功能，例如抗体和补体依赖性细胞毒性。在靶向其独特的 CD22 表位后，hHB22.7 将刺激细胞凋亡途径，使其成为抗 NHL 的多功能药物。将在滤泡性 NHL 患者队列中评估 125、250、500 或 1000 mg/m2 hHB22.7 抗 CD22 mAb 的安全性、毒性和药代动力学。患者将接受 4 剂 hHB22.7。这项研究将生成 hHB22.7 的第一个临床数据。将获得 hHB22.7 免疫疗法的初步疗效数据，并将确定未来研究中使用的 hHB22.7 剂量。这项l/ll期临床研究将为hHB22.7未来的临床研究和开发铺平道路。外行语言声明：淋巴瘤是美国癌症相关死亡的第六大常见原因，也是少数几种发病率不断增加的恶性肿瘤之一。需要新的疗法来对抗这种疾病。 HHB22.7是一种可以特异性靶向淋巴瘤的抗体。我们在小鼠研究中证明 hHB22.7 可以杀死淋巴瘤细胞，并确定了 hHB22.7 的工作原理。抗体疗法具有疗效潜力且无太大毒性，因为该抗体专门针对淋巴瘤。这项临床研究旨在了解 hHB22.7 是否安全，以及是否有足够的前景进行更多的临床试验。