SBIR PHASE I - TOPIC 405 - PROJECT TITLE: IN VIVO PHARMACOTYPING OF COMBINATION THERAPY IN PRIMARY BRAIN TUMORSFIRM FIXED PRICE - POP: 09/16/2020 - 0

SBIR 第一阶段 - 主题 405 - 项目名称：原发性脑肿瘤联合疗法的体内药型确定固定价格 - POP：09/16/2020 - 0

• 批准号: 10280953
• 负责人: CHRISTIAN KNOOPKE
• 金额: $ 40万
• 依托单位: LODESTONE BIOMEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2021-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10280953
• 关键词: Binding; Biological Models; Biosensor; Brain; Brain Glioblastoma; Brain Neoplasms; Cells; Combined Modality Therapy; Confidence Intervals; Devices; Enzyme-Linked Immunosorbent Assay; FDA approved; Glioblastoma; Immunocompetent; Immunotherapy; In Vitro; Investigation; MGMT gene; Magnetic nanoparticles; Measurement; Microdialysis; Modeling; Monitor; Mus; Oncogenic; Patients; Performance; Phase; Phenotype; Price; Primary Neoplasm; Procedures; Quality Control; Resistance; Safety; Small Business Innovation Research Grant; System; Technology; Therapeutic; Time; Tumor-Derived; base; design; immunogenic; in vivo; response; specific biomarkers; targeted biomarker; temozolomide; treatment response; tumor; tumor-immune system interactions

Lodestone Biomedical’s Immunotherapy Response Indication System (IRIS) interrogates the binding states of functionalized magnetic nanoparticles (fMNPs) localized in biosensor probes for direct in vivo longitudinal monitoring of therapeutic responses in the patient tumor immune microenvironment (TIME). Herein, we propose to commercialize the IRIS platform technology for pharmacotyping immunotherapies and temozolomide (TMZ) in glioblastoma multiforme (GBM) brain tumors. IRIS technology offers the potential for direct in vivo pharmacotyping capable of differentiating phenotypic responses across ultimately numerous tumor-derived oncogenic and immunogenic factors. This Phase 1 project directly validates the IRIS platform device measurements of target binding sensitivity to singleplex fMNP pairs in solution vs standard ELISA via Bland-Altman plot analysis, with a go-no-go requirement for >95% CI. The potential for IRIS platform technology will be demonstrated across a restricted subset of target specific biosensors in the well- characterized GBM model system, as well as appropriately pharmacotyping responsiveness to TMZ in more diverse MGMT positive and negative patient derived tumor lines. Finally, preliminary investigations of safety and proof of concept will be demonstrated in real time, localized, in vivo GBM pharmacotyping of combination therapy. Ultimately, IRIS technology will bring reliable indicators of therapeutic responsiveness with a practical implementation to the patient bedside.

Lodestone生物医学的免疫疗法反应指示系统（IRIS）询问在生物传感器问题中定位在生物传感器问题中的功能化磁性纳米颗粒（FMNP）的结合状态，以直接在体内纵向监测患者肿瘤免疫微微环境中的治疗性纵向监测（时间）。在此，我们建议在胶质母细胞瘤（GBM）脑部虹膜技术中商业化用于药物型型免疫疗法和替莫唑胺（TMZ）的IRIS平台技术，为直接In Vivo Pharmacotyping提供了潜在的潜力，能够在最终跨多种肿瘤的过度肿瘤源性和免疫源性因素中与最终的表型反应。该阶段1项目通过Bland-Altman图分析直接验证了解决方案与标准ELISA中目标结合敏感性的IRIS平台设备测量值，并具有> 95％CI的GO-NO-GO要求。在良好的GBM模型系统中，将在目标特定生物传感器的受限子集中证明IRIS平台技术的潜力，以及在更长的MGMT阳性和负面患者衍生的肿瘤系中对TMZ的适当药物分型响应能力。最后，将实时研究对安全性和概念证明的初步研究，并将组合疗法的体内GBM药物分类。最终，IRIS技术将为患者的床边带来可靠的热响应指标，并实施实际实施。