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

口腔癌是一种罕见的癌症，是发病率和死亡率的重要原因。几乎一半的口腔癌被诊断为晚期，转移和复发的口腔癌患者的5年生存率低得令人沮丧，只有27.8%。目前的治疗方案在控制转移扩散方面并不有效，并会产生显著的副作用。我们在放射肿瘤学和癌症免疫治疗中发现了一种基于纳米级金属有机框架(NMOF)的颠覆性技术。与免疫调节剂结合的nMOF作为可激活的免疫疗法用于个性化癌症疫苗接种。在X射线照射下，nMOF从癌细胞中释放出危险相关的分子模式和肿瘤抗原，并提供免疫调节剂作为病原体相关的分子模式，以增强先天性和获得性免疫反应。与检查点抑制剂相结合，nMOF可以根除局部已治疗的肿瘤，并使远处未治疗的肿瘤退化。我们将改进这项技术，并确定具有最佳疗效和最低毒性的铅配方，用于治疗复发和转移性口腔癌。这笔赠款将使我们能够在两年内确定研究性新药使能研究的主要候选人。

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.