Advancing a Glioma Immunotherapy

推进神经胶质瘤免疫治疗

基本信息

批准号：
8454188
负责人：
Dwaine Franklin Emerich
金额：
$ 98.14万
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 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8454188
关键词：
Accounting Address Adult Adverse effects Appearance Biological Brain Cell physiology Cells Cessation of life Clinical Clinical Protocols Clinical Trials Data Dendritic Cells Development Devices Disease Disease remission Education Effectiveness Elements Equipment Family suidae Glioblastoma Glioma Goals Granulocyte-Macrophage Colony-Stimulating Factor Guidelines Human Immune Immune response Immunotherapeutic agent Immunotherapy Implant In Situ Incidence Infiltration Inflammation Laboratories Life Malignant - descriptor Malignant Neoplasms Malignant neoplasm of brain Marshal Mediating Methods Michigan Modeling Mus Necrosis Nervous system structure Neuroglia Operative Surgical Procedures Pain Patients Performance Phase Porosity Pre-Clinical Model Preparation Procedures Process Protocols documentation Public Health Quality Control Radiation Rat Strains Rattus Reagent Recruitment Activity Regimen Research Design Running Safety Site Small Business Innovation Research Grant Sprague-Dawley Rats Technology Testing Therapeutic Effect Tissues Toxicology Transcend Treatment Cost Tumor Antigens Universities Vaccines Validation Work Writing base brain size cancer cell cancer diagnosis chemotherapy clinical efficacy cofactor cranium design implantable device implantation improved in vivo insight man manufacturing process melanoma novel phase 2 study pre-clinical programs prophylactic public health relevance research clinical testing research study safety study therapeutic vaccine tumor vaccine safety

项目摘要

DESCRIPTION (provided by applicant): A Phase II SBIR program of preclinical development is proposed for the development of an active specific immunotherapeutic called Cellarium" for treatment of glial cell-based cancers. Successful completion of this project will confirm therapeutic effect and pre-clinical safety of the vaccine in preparation for first-in-human studies Upon demonstration of safety and efficacy, the Cellarium vaccine will provide a greatly-improved, targeted treatment for glioma patients, for whom current treatments can be debilitating, painful and expensive. 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 shown increasing incidence of glioma in US adults. Gliomas are predominantly treated today with an aggressive three-step protocol of surgery, chemotherapy and radiation. Despite this regimen, 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. Originally, this technology approach was conceived in the laboratory of Dr. David Mooney at the University of Michigan (who is now at Harvard University). The Cellarium technology is the result of work at InCytu in both the melanoma and glioma models that has led to new insights which transcend the original discoveries at Michigan and Harvard and have led to a more effective and reliable product. The Cellarium is an in situ therapeutic vaccine which incorporates 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 strong, targeted immune response against malignant tissue. Phase II aims are: (1) to manufacture Cellarium using equipment and methods purpose designed to yield CNS specific product sized for both the murine and human sized brain and confirm Phase I results of the Cellarium for Glioma in both murine and porcine preclinical models ; (2) to develop formal Standard operating Procedures needed for submission to the FDA and validate manufacture and QC of the devices then perform a pre-GLP study needed for discussions with the FDA; (3) to conduct GLP safety and efficacy study in preparation for the filing of an IND. If Phase II studies are successful, the Cellarium" vaccine will continue to be developed through clinical trials with the eventual goal of scaling manufacture in the US and selling as a commercially available specific immunotherapeutic vaccine to treat glioma patients.

描述（由申请人提供）：临床前开发的 II 期 SBIR 计划旨在开发一种名为 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确认治疗效果和临床前效果疫苗的安全性，为首次人体研究做准备在安全性和有效性得到证明后，Cellarium 疫苗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，对于这些患者来说，目前的治疗方法可以神经胶质瘤是一种使人衰弱、痛苦且昂贵的致命疾病，在美国，2009 年诊断出的 22,070 例脑癌和其他神经系统癌症中，有 44% 是由神经胶质瘤引起的。最近的研究表明，神经胶质瘤的死亡人数不断增加。目前，美国成人胶质瘤的发病率主要采用积极的三步疗法：手术、化疗和放疗。尽管采用了这种治疗方案，多形性胶质母细胞瘤 (GBM)（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。最初，这种技术方法是在密歇根大学（现就职于哈佛大学）David Mooney 博士的实验室中构想出来的。 Cellarium 技术是 InCytu 在黑色素瘤和神经胶质瘤模型方面的工作成果，它带来了超越密歇根州和哈佛大学最初发现的新见解，并带来了更有效和更可靠的产品。 Cellarium 是一种原位治疗性疫苗，融合了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，然后释放它们以针对恶性组织产生强烈的、有针对性的免疫反应。第二阶段的目标是：(1) 使用旨在生产适合小鼠和人类大脑大小的中枢神经系统特定产品的设备和方法来制造 Cellarium，并在小鼠和猪临床前模型中确认 Cellarium 用于神经胶质瘤的第一阶段结果； (2) 制定提交给 FDA 所需的正式标准操作程序，并验证设备的制造和质量控制，然后进行与 FDA 讨论所需的预 GLP 研究；（3）开展GLP安全性和有效性研究，为IND申报做准备。如果二期研究成功，Cellarium”疫苗将继续通过临床试验进行开发，最终目标是在美国扩大生产规模，并作为市售特异性免疫治疗疫苗销售，用于治疗神经胶质瘤患者。