Primers: Combining Radiotherapy and Immunotherapy using next genertaion radiotherapy biomaterials

引物：使用下一代放射治疗生物材料结合放射治疗和免疫治疗

• 批准号: 9302964
• 负责人: Wilfred Ngwa
• 金额: $ 22.92万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302964
• 关键词: Adverse effects; Antigens; Award; Biocompatible Materials; Biodistribution; C57BL/6 Mouse; CD8-Positive T-Lymphocytes; Cancer Patient; Cancer Vaccines; Cells; Cessation of life; Custom; Cytotoxic T-Lymphocytes; Dendritic Cells; Development; Disease; Distant; Dose; Electrons; Ensure; Enzyme-Linked Immunosorbent Assay; Exposure to; Fluorescence; Fright; Goals; Gold; Grant; Granulocyte-Macrophage Colony-Stimulating Factor; Immune; Immune response; Immune system; Immunologic Adjuvants; Immunologic Memory; Immunotherapy; Implant; In Situ; In Vitro; Infiltration; Irradiated tumor; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Measures; Mediating; Memory; Metastatic Prostate Cancer; Methods; Mus; Neoplasm Metastasis; Newly Diagnosed; Normal tissue morphology; Outcome; Pancreas; Patient-Focused Outcomes; Patients; Polymers; Pre-Clinical Model; Public Health; Quality of life; Radiation; Radiation Oncologist; Radiation therapy; Radiation-Sensitizing Agents; Radioresistance; Recruitment Activity; Resources; Risk; Schedule; Site; Survival Rate; T cell differentiation; T cell response; TNFRSF5 gene; Technology; Testing; Time; Tissues; Toxic effect; Treatment Efficacy; Tumor Antigens; Tumor Cell Line; United States National Institutes of Health; Vaccines; Weight; Work; X-Ray Computed Tomography; biodegradable polymer; cancer recurrence; cell killing; cohort; controlled release; design; fighting; high reward; in vivo; innovation; killings; lung metastatic; lymph nodes; mouse model; nanoparticle; neoplastic cell; novel strategies; prevent; radioresistant; radiosensitizing; response; subcutaneous; treatment response; tumor; uptake

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.

项目摘要 转移占所有相关痛苦和死亡的癌症的90％以上，可以说 提出了癌症管理中最巨大的挑战。中央创新和 该项目的总体目标是开发新设计放疗生物材料 可以用来显着提高胰腺/肺/前列腺癌治疗率：包括 转移和克服放射线的治疗，所有这些都没有给您带来任何不便 患者。新的生物材料旨在简单地取代惰性生物材料 （基准/间隔者），目前已逐渐植入以确保空间精度 放疗。这些新的生物材料专门纳入了无毒目标的有效载荷 可生物降解聚合物中的放射敏金纳米颗粒（GNP）和免疫辅助 矩阵。到位后，新设计的生物材料将有效载荷直接释放到 作为聚合物的肿瘤降解。在放射疗法期间，释放的GNP将显着 增强局部肿瘤细胞杀死，通过 爱因斯坦的光电效应，对健康组织的毒性很小。平均抗原来自 辐照的肿瘤细胞与释放的免疫辅助剂一起工作，以促进稳健的T细胞反应， 这可能杀死远离辐照部位的转移细胞（脱离效应）并建立 免疫记忆以防止癌症复发。有效载荷的原位释放慢将最小化 系统性/重叠的毒性，目前是竞争的关键障碍/关注 方法。总体而言，我们的低风险，潜在的高回报创新可能会大大增强 胰腺/UNG/前列腺癌患者的生存和生活质量。