Nanoscale Metal-Organic Frameworks as X-ray Activatable Cancer Vaccines

纳米级金属有机框架作为 X 射线激活癌症疫苗

• 批准号: 10558960
• 负责人: ZE-QI XU
• 金额: $ 30万
• 依托单位: COORDINATION PHARMACEUTICALS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-20 至 2023-01-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10558960
• 关键词: Cancer Vaccines; Diagnosis; Distant; Drug Kinetics; Formulation; Grant; Immune checkpoint inhibitor; Immune response; Immunomodulators; Immunotherapeutic agent; Investigational Drugs; Lead; Mediating; Metals; Metastatic/Recurrent; Molecular; Morbidity - disease rate; Patients; Pattern; Radiation Oncology; Recurrence; Roentgen Rays; Survival Rate; Technology; Toxicology; Treatment-related toxicity; Tumor Antigens; adaptive immune response; anti-cancer; base; cancer cell; cancer immunotherapy; cancer vaccination; lead candidate; malignant mouth neoplasm; mortality; nanoscale; pathogen; rare cancer; side effect; tumor; x-ray irradiation

Oral cancer, a rare cancer, represents a significant cause of morbidity and mortality. Almost half of oral cancers have been diagnosed in advanced stages, and the 5-year survival rate for patients with metastatic and recurrent oral cancer is dismal at 27.8%. Current treatment options are not effective in controlling metastatic spread and incur significant side effects. We discovered a disruptive technology in radiation oncology and cancer immunotherapy based on nanoscale metal-organic frameworks (nMOFs). nMOFs conjugated with immune modulators act as activable immunotherapeutics for personalized cancer vaccination. Upon X-ray irradiation, nMOFs release danger-associated molecular patterns and tumor antigens from cancer cells and deliver immune modulators as pathogen-associated molecular patterns for enhanced innate and adaptive immune responses. In combination with checkpoint inhibitors, nMOFs eradicate local, treated tumors and regress distant, untreated tumors. We will refine this technology and identify lead formulations with optimal efficacy and minimal toxicity for the treatment of recurrent and metastatic oral cancer. This grant will allow us to identify a lead candidate for Investigational New Drug-enabling studies in two years.

口腔癌是一种罕见的癌症，是发病率和死亡率的重要原因。几乎一半的口腔癌在晚期被诊断出来，转移性和复发性口腔癌患者的5年生存率低至27.8%。目前的治疗方案在控制转移扩散方面无效，并产生显著的副作用。我们发现了一种基于纳米级金属有机框架（nMOFs）的放射肿瘤学和癌症免疫治疗的颠覆性技术。与免疫调节剂缀合的nM0F充当用于个性化癌症疫苗接种的可活化免疫治疗剂。在X射线照射时，nMOF从癌细胞释放病原体相关的分子模式和肿瘤抗原，并递送免疫调节剂作为病原体相关的分子模式，用于增强先天性和适应性免疫应答。与检查点抑制剂组合，nMOFs根除局部治疗的肿瘤并使远处未治疗的肿瘤消退。我们将完善这项技术，并确定具有最佳疗效和最小毒性的领先配方，用于治疗复发性和转移性口腔癌。这笔赠款将使我们能够在两年内确定一个主要候选人进行新药研究。