Reducing Complement Inhibition to Treat Leukemia and Lymphoma

描述(申请人提供)：这项申请的资金将把白血病和淋巴瘤的一种新的癌症联合疗法推向人类临床试验。单抗，即“单抗”，已经成为一种迅速增长的肿瘤治疗方法。尽管它们在某些临床应用中取得了成功，但单抗的治疗效果有限，只有一小部分患者对这些药物做出了自己的治疗反应。越来越明显的是，许多肿瘤通过利用人体自身的免疫调节系统来逃避成功的消除。这些相同的机制也降低了单抗的抗癌效果。我们正在开发一种分子，以解决这些关键机制之一，通过以下方式提高mAbs的治疗效果：1)提高癌症对治疗的敏感性；2)揭示耐药癌症，使其再次变得敏感；以及3)可能允许治疗已变得难以治疗的癌症。这可以使单抗治疗更有效，并有可能减少治疗所需的单抗数量，从而降低成本和潜在的副作用。改进利妥昔单抗治疗对公共卫生的影响是显著的。有300,000多名非霍奇金淋巴瘤(NHL)患者，大多数接受利妥昔单抗单独或与化疗联合治疗。许多患者出现复发疾病，NHL的5年生存率为63%。在大多数肿瘤复发的病例中，患者对利妥昔单抗治疗产生抵抗力。这项研究的直接目标是收集数据，以便能够提交淋巴瘤联合疗法的研究新药(IND)。我们在华盛顿大学的顾问收集了大量信息，支持去除细胞表面CD46与抗体治疗相结合治疗血癌的优越性。我们的长期目标是将这项技术从研究平台转化到临床床边，从而加强单抗(MAb)治疗。

DESCRIPTION (provided by applicant): Funding of this application will move a new combination cancer therapy for leukemia and lymphomas towards human clinical trials. Monoclonal antibodies, "mAbs" have emerged as a rapidly growing class of oncology therapeutics. Despite their success in certain clinical applications, the therapeutic efficacy of mAbs is limited, with only a minority of patients responding to these agents as therapies on their own. It is becoming clear that many tumors evade successful elimination by co-opting the body's own immune regulatory systems. These same mechanisms also reduce the anti-cancer effects of mAbs. We are developing a molecule that addresses one of these key mechanisms that improves the therapeutic effects of mAbs by: 1) increasing sensitivity of cancers to treatment; 2) unmasking resistant cancers so they again become sensitized; and 3) possibly allowing treatment of cancers that have become refractory to therapy. This could make mAb therapy more effective, and potentially reduce the amounts of mAbs required for treatment, thus reducing costs and potential side effects. The public health implications of improving rituximab treatment are significant. There are over 300,000 patients with non-Hodgkins lymphoma (NHL), and the majority receives treatment with rituximab either alone or combined with chemotherapy. Many patients develop recurrent diseases, and 5-year survival rates for NHL is 63%. In most cases of tumor recurrence, patients develop resistance to rituximab therapy. The immediate goal of the research is to collect data to enable an Investigational New Drug (IND) filing on a combination therapy for lymphoma. Our consultant at the University of Washington has collected a significant body of information supporting the superiority of the combination of depleting CD46 on the cell surface with antibody therapy in blood cancers Our long-term goal is to translate the technology from research bench to clinical bedside leading to enhancement of monoclonal antibody (mAb) therapy.