iPS cell based immunotherapy for malignant gliomas

基于 iPS 细胞的恶性胶质瘤免疫疗法

• 批准号: 8557091
• 负责人: John Park
• 金额: $ 107.36万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8557091
• 关键词: Antitumor Response; Bioluminescence; Brain Neoplasms; Cells; Clinical; Clinical Treatment; Clinical Trials; Control Animal; Effector Cell; Excision; Glioblastoma; Glioma; Goals; Human; Image; Immune; Immune system; Immunotherapy; Implant; Injection of therapeutic agent; Malignant Glioma; Measures; Methods; Microglia; Modeling; Monitor; Mouse Cell Line; Mus; Newborn Animals; Operative Surgical Procedures; Patients; Phase; Primary Brain Neoplasms; Process; Protocols documentation; Radiation; Regimen; Survival Rate; Teratoma; Translating; Treatment Protocols; Vaccination; base; blastocyst; chemotherapy; fighting; induced pluripotent stem cell; interest; outcome forecast; standard care; temozolomide; treatment strategy; tumor; tumor growth

We have established a syngeneic mouse brain tumor model in which tumor growth or disappearance can be easily monitored using bioluminescence imaging. We have successfully treated tumors with microglia obtained from neonatal animals as proof of principle that a microglial treatment strategy may be effective. On average, treated groups achieve a long term survival rate of 60%-70% whereas control animals routinely achieve a 0% long term survival rate. We have created iPS cell lines from mice syngeneic to those implanted with tumors and have fully characterized their multipotency using teratoma formation and blastocyst injections. We have developed a protocol for differentiating the iPS cells into microglia and are in the process of characterizing these cells to confirm their microglial identity. Methods that are effective in the treatment of our mouse tumors will be translated to the human setting.

我们已经建立了一种合成小鼠脑肿瘤模型，其中可以使用生物发光成像轻松监测肿瘤的生长或消失。 我们已经用从新生动物获得的小胶质细胞成功治疗了肿瘤，以证明小胶质细胞治疗策略可能是有效的。 平均而言，经过处理的组达到60％-70％的长期存活率，而对照动物通常达到0％的长期存活率。 我们已经创建了来自小鼠的IPS细胞系到植入肿瘤的小鼠的IPS细胞系，并使用畸胎瘤形成和胚泡注射充分表征了它们的多能力。我们已经开发了一种将IPS细胞区分为小胶质细胞的方案，并正在表征这些细胞以确认其小胶质细胞身份。 有效治疗小鼠肿瘤的方法将转化为人类环境。