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

描述(申请人提供)：本次L/11期临床试验采用了独特的新的抗CD22单抗人源化HB22.7(hHB22.7)。HHB22.7的开发得到了NCI的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)细胞的凋亡。HHB22.7有可能成为治疗非霍奇金淋巴瘤的新方法。我们开发抗非霍奇金淋巴瘤单抗的方法是通过关注由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，识别受体参与的最终生理后果为受体操纵和开发新的有效药物奠定了基础。使用mHB22.7的出色临床前结果促使我们继续进行hHB22.7的临床试验。人源化的HB22.7将允许招募免疫功能，如抗体和补体依赖的细胞毒性。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。125、250、500或1000 mg/m2的hHB22.7抗CD22单抗的安全性、毒性和药代动力学将在滤泡性NHL患者队列中进行评估。患者将接受4剂hHB22.7。这项研究将产生第一个hHB22.7的临床数据。将获得hHB22.7免疫治疗的初步疗效数据，并将确定在未来研究中使用的hHB22.7剂量。本次L/11期临床研究将为hHB22.7的进一步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上升的恶性肿瘤之一。需要新的治疗方法来对抗这种疾病。HHB22.7是一种可以特异性靶向淋巴瘤的抗体。我们已经在小鼠的研究中证明了hHB22.7可以杀死淋巴瘤细胞，并确定了hHB22.7的作用方式。抗体疗法有可能在没有太大毒性的情况下有效，因为抗体专门针对淋巴瘤。这项临床研究旨在确定hHB22.7是否安全，并有足够的前景进行更多的临床试验。

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.