Novel Immunotherapy for Brain Cancer

描述(申请人提供)：胶质母细胞瘤是成人最常见的原发脑肿瘤。虽然许多患者在手术切除、放射治疗和化疗后病情得到缓解，但这种缓解是短暂的，而且总是伴随着肿瘤的复发和进展。未能为胶质母细胞瘤患者提供持久的治疗方法反映了这种癌症的复杂性。涉及单抗的靶向治疗在包括癌症在内的各种疾病中取得了显着的成功。不幸的是，目前针对胶质母细胞瘤的靶向治疗贝伐单抗的临床结果令人失望。显然需要针对胶质母细胞瘤的替代靶向治疗，以潜在地提高新诊断患者的总体存活率。这项提议旨在进一步开发一种针对癌症特异性抗原的抗体，该抗原已在人类身上显示出有希望的临床结果。我们将探索非岩藻糖化单抗变体在体外增强ADCC活性的可能性，这最终将转化为动物模型中更好的治疗效果。这项研究将是第一次在脑部恶性肿瘤的背景下评估非岩藻糖基化的mAb。

DESCRIPTION (provided by applicant): Glioblastoma is the most common primary brain tumor in adults. While many patients achieve disease remission following treatment with surgical resection, radiation therapy and chemotherapy, this remission is brief and invariably followed by tumor recurrence and progression. The failure to offer durable therapies to patients with glioblastoma reflects the complex nature of this cancer. Targeted therapies involving monoclonal antibodies (mAbs) have had remarkable success in various diseases including cancer. Unfortunately, the current targeted therapy for glioblastoma, bevacizumab, has had disappointing clinical results. There is a clear need for alternative targeted therapies for glioblastoma that can potentially improve overall survival of newly diagnosed patients. This proposal is intended to further develop an antibody against a cancer-specific antigen that has shown promising clinical results in humans. We will be exploring the possibility that the non-fucosylated mAb variant will have enhanced ADCC activity in vitro that will ultimately translate into enhanced therapeutic benefit in animal models. This research will be the first time that a non-fucosylated mAb will be evaluated in the context of brain malignancy.