Primers: Combining Radiotherapy and Immunotherapy using next genertaion radiotherapy biomaterials

项目摘要 转移占所有癌症相关痛苦和死亡的90%以上， 这是癌症治疗中最大的挑战。核心创新和 该项目的总体目标是开发新设计的放射治疗生物材料， 可用于显著提高胰腺癌/肺癌/前列腺癌的治愈率：包括 治疗转移和克服放射抵抗，所有这些都没有额外的不便， 患者新的生物材料被设计成简单地取代惰性生物材料 （基准点/间隔器），目前常规植入，以确保手术期间的空间准确性。 放疗这些新的生物材料特别结合了无毒的靶向有效载荷， 放射增敏金纳米颗粒（GNP）和生物可降解聚合物中的免疫佐剂 矩阵一旦就位，新设计的生物材料可控制地将有效载荷直接释放到 肿瘤随着聚合物的降解。在放射治疗期间，释放的GNP将显著增加 增强局部肿瘤细胞杀伤，通过以下途径显著增加对放射抗性肿瘤细胞的剂量： 爱因斯坦的光电效应，对健康组织的毒性最小。与此同时， 辐射的肿瘤细胞与释放的免疫佐剂一起作用以引发强有力的T细胞应答， 其可以杀死远离照射部位的转移细胞（远位效应）并建立 免疫记忆防止癌症复发。在现场缓慢释放有效载荷将最大限度地减少 全身性/重叠毒性，目前是竞争药物的关键障碍/问题 接近。总的来说，我们的低风险，潜在的高回报创新可以显着提高 胰腺癌/肺癌/前列腺癌患者的生存率和生活质量。

Project Summary Metastasis accounts for over 90% of all cancer associated suffering and death, and arguably presents the most formidable challenges in cancer management. The central innovation and overall goal of this project is the development of new design radiotherapy biomaterials that could be employed to significantly boost pancreatic/lung/prostate cancer cure rate: including treatment of metastasis and overcoming radioresistance, all at no additional inconvenience to patients. The new biomaterials are designed to simply replace the inert biomaterials (fiducials/spacers), which are currently routinely implanted to ensure spatial accuracy during radiotherapy. These new biomaterials specifically incorporate a payload of non-toxic targeted radiosensitizing gold nanoparticles (GNP), and immunoadjuvants in a biodegradable polymer matrix. Once in place, the new design biomaterials controllably release the payload directly into the tumor as the polymer degrades. During radiotherapy, the released GNP will significantly enhance local tumor cell kill, substantially boosting dose to radioresistant tumor cells via Einstein’s photoelectric effect, with minimal toxicity to healthy tissue. Meanwhile, antigens from irradiated tumor cells work with the released immunoadjuvant to prime a robust T cell response, which may kill metastatic cells distant from the irradiated site (abscopal effect) and establish immune memory to prevent cancer recurrence. Slow in-situ release of the payload will minimize systemic/overlapping toxicities, which are currently a critical barrier/concern with competing approaches. Overall, our low risk, potential high-reward innovation could significantly enhance survival and quality of life for pancreatic/ung/prostate cancer patients.