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 Biomedical 的免疫治疗反应指示系统 (IRIS) 询问位于生物传感器探针中的功能化磁性纳米颗粒 (fMNP) 的结合状态，用于直接体内纵向监测患者肿瘤免疫微环境 (TIME) 中的治疗反应。在此，我们建议将 IRIS 平台技术商业化，用于多形性胶质母细胞瘤 (GBM) 脑肿瘤的药物分型免疫疗法和替莫唑胺 (TMZ)。 IRIS 技术提供了直接体内药型分析的潜力，能够区分最终众多肿瘤衍生的致癌和免疫原性因素的表型反应。该第一阶段项目通过 Bland-Altman 图分析直接验证 IRIS 平台设备对溶液中单重 fMNP 对的靶标结合敏感性与标准 ELISA 的测量结果，并要求 CI > 95%。 IRIS 平台技术的潜力将在特征明确的 GBM 模型系统中的目标特异性生物传感器的有限子集上得到证明，以及在更多样化的 MGMT 阳性和阴性患者来源的肿瘤系中对 TMZ 的适当药型分型反应。最后，安全性的初步研究和概念验证将在联合治疗的实时、局部、体内 GBM 药型分析中得到证实。最终，IRIS 技术将通过在患者床边的实际实施带来可靠的治疗反应指标。