Novel Immunotherapy for Brain Cancer

脑癌的新型免疫疗法

• 批准号: 8833722
• 负责人: Andrew C Hiatt
• 金额: $ 22.5万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833722
• 关键词: Adult; Anaplastic astrocytoma; Animal Model; Antibodies; Antibody Therapy; Antigens; Binding; Biological Products; Biology; Brain; Breast; Cancer Patient; Cells; Cervical; Clinical; Clinical assessments; Complex; Disease; Disease remission; Epitopes; Excision; Failure; Fucose; Future; Glioblastoma; Glioma; Growth; Health; Histology; Human; Immune; Immune system; Immunotherapy; In complete remission; Indium; Japan; Licensing; Lung; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Malignant neoplasm of cervix uteri; Mediator of activation protein; Molecular Genetics; Monoclonal Antibodies; Mus; Nature; Newly Diagnosed; Nicotiana; Normal Cell; Normal tissue morphology; Operative Surgical Procedures; Ovarian; Pancreas; Patients; Phase; Plants; Polysaccharides; Primary Brain Neoplasms; Radiation therapy; Recording of previous events; Recurrence; Research; Specificity; Stomach; Structure; Surface; Survival Rate; System; Therapeutic; Time; Translating; Variant; Vimentin; Virus; Xenograft Model; Xylose; antibody-dependent cell cytotoxicity; base; bevacizumab; brain cell; brain tissue; cancer cell; chemotherapy; improved; in vitro activity; novel; outcome forecast; partial response; public health relevance; research clinical testing; respiratory; success; therapeutic target; tumor

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.

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。虽然许多患者在接受手术切除、放射治疗和化疗后获得疾病缓解，但这种缓解是短暂的，并且总是会出现肿瘤复发和进展。未能为胶质母细胞瘤患者提供持久治疗反映了这种癌症的复杂性。涉及单克隆抗体（mAb）的靶向疗法在包括癌症在内的多种疾病中取得了显着的成功。不幸的是，目前胶质母细胞瘤的靶向治疗贝伐珠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疗法，以潜在地提高新诊断患者的总体生存率。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 变体在体外增强 ADCC 活性的可能性，这最终将转化为动物模型中增强的治疗效果。这项研究将是首次在脑恶性肿瘤的背景下评估非岩藻糖基化单克隆抗体。