Novel Immunotherapy for Brain Cancer

描述（由申请人提供）：胶质母细胞瘤是成人中最常见的原发性脑肿瘤。虽然许多患者在手术切除、放疗和化疗治疗后达到疾病缓解，但这种缓解是短暂的，并且总是伴随着肿瘤复发和进展。未能为胶质母细胞瘤患者提供持久的治疗反映了这种癌症的复杂性。涉及单克隆抗体（mAb）的靶向治疗在包括癌症在内的各种疾病中取得了显著的成功。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。对于胶质母细胞瘤的替代靶向疗法存在明确的需求，其可以潜在地改善新诊断患者的总生存期。该提案旨在进一步开发针对癌症特异性抗原的抗体，该抗体已在人类中显示出有希望的临床结果。我们将探索非岩藻糖基化mAb变体在体外具有增强的ADCC活性的可能性，这将最终转化为动物模型中增强的治疗益处。这项研究将是首次在脑恶性肿瘤的背景下评价非岩藻糖基化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.