Immunotherapeutic Biomaterials for Treatment of Glioma

用于治疗神经胶质瘤的免疫治疗生物材料

基本信息

批准号：
8002576
负责人：
Dwaine Franklin Emerich
金额：
$ 33.32万
依托单位：
IN CYTU, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8002576
关键词：
Accounting Acute Address Adjuvant Adjuvant Chemotherapy Adult Adverse effects Affect Animals Antigens Applied Research Benchmarking Biocompatible Materials Biological Biomedical Engineering Bolus Infusion Brachytherapy Brain Brain Neoplasms Budgets Cancer Vaccines Cancerous Cell physiology Cells Cellular Immunity Cessation of life Characteristics Clinical Clinical Trials Cyclic GMP Cytotoxic T-Lymphocytes Data Dendritic Cells Dendritic cell activation Development Devices Disease Distant Dose Drug Formulations Education Engineering Excision Expenditure FDA approved Foreign Bodies Foundations Funding Glioblastoma Glioma Goals Granulocyte-Macrophage Colony-Stimulating Factor Hair Healthcare Systems Human Immune Immune Cell Activation Immune Targeting Immune response Immune system Immunity Immunization Immunosuppressive Agents Immunotherapeutic agent Implant In Situ Incidence Infection Infiltration Injection of therapeutic agent Injury Intellectual Property Lead Licensing Life Malignant - descriptor Malignant Glioma Malignant Neoplasms Malignant neoplasm of brain Marshal Mediating Melanoma Vaccine Modality Modeling Mus Nature Nervous system structure Neuroglia Oligonucleotides Pain Pathway interactions Patients Phase Physicians Polymers Porosity Pre-Clinical Model Preparation Production Protocols documentation Qualifying Radiation therapy Rattus Reaction Recruitment Activity Regimen Regulatory T-Lymphocyte Research Safety Sales Schools Signal Transduction Site Small Business Innovation Research Grant System T-Lymphocyte Technology Testing Therapeutic Time TimeLine Tissues Toxic effect Treatment Cost Tumor Antigens Universities Vaccine Design Vaccine Therapy Vaccines Work base biomaterial compatibility cancer cell cancer diagnosis cofactor cost cytokine implantation improved in vivo in vivo Model macrophage manufacturing facility melanoma novel novel strategies outcome forecast phase 1 study physical property poly(lactide)pre-clinical preclinical study prevent professor programs prophylactic public health relevance research clinical testing response scaffold spatiotemporal stem subcutaneous trafficking trend tumor vaccine development vaccine efficacy vaccine safety

项目摘要

DESCRIPTION (provided by applicant): A Phase I SBIR program of preclinical development is proposed focusing on the development of an active specific immunotherapeutic called Cellarium" for treatment of glial cell-based cancers. Successful completion of this project will establish the minimum level of therapeutic feasibility and lead to further development of the vaccine in preparation for first-in-human studies. Upon demonstration of safety and efficacy, Cellarium would provide a greatly- improved, targeted treatment for glioma patients, which currently have dismal survival prognosis, are expensive to treat, and for whom current treatments can be debilitating and painful. Gliomas are widespread deadly diseases for which current therapies are inadequate. In the US gliomas accounted for 44% of the 22,070 cases of brain and other nervous system cancers diagnosed and 12,920 associated deaths in 2009. Recent studies have also shown trends toward increased incidence of glioma in US adults. Currently, gliomas are predominantly treated with an aggressive three step protocol. Despite this regime, patients with Glioblastoma Multiforme (GBM), the most common and deadly malignant brain tumor, still have a median survival of less than 15 months. Moreover, the estimated cost of treatment for each patient with a malignant brain tumor ranges from $30,000 to several hundred thousand dollars annually. Based on the Cellarium" technology platform developed at Harvard University, this in situ vaccine, which incorporates well-established biological cofactors and patient specific cell lysate, attracts dendritic cells (DCs), exposes them to the tumor specific antigens, and then releases them to direct a bolstered, targeted immune response against malignant tissue. Support is requested to refine vaccine formulation and demonstrate initial efficacy and safety in an in vivo therapeutic glioma model, an in vivo tumor resection model8 and biocompatibility studies. If Phase I studies are successful, the Cellarium vaccine will continue to be developed for clinical trials which the eventual goal being scaled manufacture in the US and sale as a commercially available specific immunotherapeutic vaccine to treat glioma patients. PUBLIC HEALTH RELEVANCE: We propose to develop an active specific immunotherapeutic vaccine that helps the body's own immune system identify and then attack cancerous glial cells. This device, if validated, could give physicians and their patients a much needed therapy prolong survival and improve treatment of glioma, a disease which currently affects around 21,560 US citizens, has a 15 month median survival time and can be both painful and harmful to treat. Furthermore, this therapy would offer a significant cost reduction to the health care system by not only supplanting the need for the current, expensive treatment regimes but also preventing additional expenditures that stem from the side effects of current treatments.

描述（由申请人提供）：提出了临床前开发的 I 期 SBIR 计划，重点是开发一种名为 Cellarium 的活性特异性免疫疗法，用于治疗基于神经胶质细胞的癌症。该项目的成功完成将建立最低水平的治疗可行性，并导致进一步开发该疫苗正在为首次人体研究做准备，在证明安全性和有效性后，Cellarium 将为神经胶质瘤患者提供一种大大改进的、有针对性的治疗，这些患者目前的生存预后不佳，治疗费用昂贵。神经胶质瘤是一种普遍存在的致命疾病，在美国，2009 年诊断出的 22,070 例脑癌和其他神经系统癌症病例中，有 44% 是由神经胶质瘤引起的，其中 12,920 人因此死亡。研究表明，美国成人神经胶质瘤的发病率呈上升趋势。目前，神经胶质瘤主要采用积极的三步疗法进行治疗。尽管采取了这种治疗方案，多形性胶质母细胞瘤 (GBM) 这种最常见和致命的恶性脑肿瘤患者的中位生存期仍然不足 15 个月。此外，预计每位恶性脑肿瘤患者的治疗费用每年从 3 万美元到数十万美元不等。这种原位疫苗基于哈佛大学开发的“Cellarium”技术平台，融合了成熟的生物辅助因子和患者特异性细胞裂解物，吸引树突状细胞（DC），将其暴露于肿瘤特异性抗原，然后将其释放到需要支持对恶性组织进行增强的、有针对性的免疫反应，以改进疫苗配方，并在体内治疗性神经胶质瘤模型、体内肿瘤切除模型8和生物相容性中证明初步疗效和安全性。如果第一阶段研究成功，Cellarium 疫苗将继续开发用于临床试验，最终目标是在美国规模化生产，并作为市售的特异性免疫治疗疫苗销售，以治疗神经胶质瘤患者。公共卫生相关性：我们建议开发一种主动特异性免疫治疗疫苗，帮助人体自身的免疫系统识别并攻击癌性神经胶质细胞。如果该设备得到验证，可以为医生及其患者提供急需的治疗方法，延长患者的生存期并改善神经胶质瘤的治疗，这种疾病目前影响约 21,560 名美国公民，中位生存时间为 15 个月，治疗起来既痛苦又有害。此外，这种疗法不仅可以取代当前昂贵的治疗方案，而且还可以防止因当前治疗的副作用而产生的额外支出，从而显着降低医疗保健系统的成本。