High throughput nanoplasmonic exosome testing (NEXT) of immunotherapies in bladder cancer

膀胱癌免疫疗法的高通量纳米等离子体外泌体测试（NEXT）

• 批准号: 10463778
• 负责人: Cesar M Castro
• 金额: $ 64.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10463778
• 关键词: Anatomy; Bioinformatics; Biological Assay; Biological Markers; Biological Specimen Banks; Biology; Biomedical Engineering; Bladder; Bladder Urothelium; Cancer Detection; Cancer Patient; Cancer cell line; Charge; Clinical; Clinical Oncology; Clinical Trials; Collection; Consensus; Correlative Study; Couples Therapy; Coupling; Decision Making; Detection; Devices; Diagnostic; Generations; Genitourinary system; Glean; Graft Rejection; Guidelines; Human; Image; Image Analysis; Immune checkpoint inhibitor; Immunotherapy; Investigation; Kidney; Kidney Transplantation; Laboratories; Light; Location; Magnetism; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Messenger RNA; Molecular; Molecular Profiling; Monitor; Nanotechnology; Neoplasm Metastasis; Nucleic Acids; Oncologist; Patients; Performance; Peripheral; Pharmacodynamics; Physics; Prostate; Proteins; Protocols documentation; Reaction; Regimen; Regression Analysis; Research Personnel; Sampling; Signal Transduction; Source; Surface; System; Systems Biology; Testing; Time; Traction; Tumor Immunity; Urine; Urogenital Cancer; Ursidae Family; X-Ray Computed Tomography; base; biomarker panel; cancer therapy; cell bank; clinical imaging; effective therapy; exosome; expectation; experience; extracellular vesicles; imaging modality; improved; innovation; insight; instrumentation; liquid biopsy; multidisciplinary; nanoGold; nanometer; nanoplasmonic; novel; novel marker; personalized immunotherapy; plasmonics; pre-clinical; pressure; prospective; repository; response; sensor; tool; translational study; treatment strategy; tumor; tumor microenvironment; tumor-immune system interactions; urinary

Challenges. Once metastatic, only 5 out of 100 patients are alive at five years. Immune checkpoint inhibitors have demonstrated increasing clinical traction yet conventional imaging such as CT scans struggle to accurately assess tumor response in this treatment context. Serially accessible sources of tumor and host biomarkers could add earlier insights into response this informing timely go / no-go decision making to render precision immunotherapy. Innovation: In light of needed pre-competitive nanotechnology tools for EV investigation to fill temporal and scientific gaps precluding accurate immunotherapy-based treatment monitoring, our group developed and validated a magneto- electrochemical platform without need for EV purification and capable of 96 parallel readouts within 45 minutes. This proposal exploits the bladder's intimate anatomical location within the genitourinary system; urine would thus provide us with rich repositories of bladder cancer EVs. We previously demonstrated feasibility of urine EV testing in kidney transplant rejection. Through increased excited charges generated by inducing plasmonic resonance in gold nanoparticles, we recently accelerated electrochemical reactions within our most current and scalable platform to achieve 12-fold signal increase from EV surface markers. We hypothesize that advancing our nanoplasmonic EV sensor for human urine and optimizing assay protocols to measure intra-EV and surface markers, could identify high value bladder cancer and host biomarkers (protein and mRNA) to better examine their interplay over time and under treatment pressures. We propose three specific aim: AIM 1: To optimize our nanoplasmonic sensor (NEXT) assay and instrumentation for high-throughput urine-based analyses and comprehensive profiling of both surface and intra-EV markers. AIM 2: To employ pre-clinical and banked biospecimens for NEXT analyses to examine profiling performance and inform optimal biomarker panel. AIM 3: Use NEXT to prospectively monitor and profile urinary EVs from patients undergoing immunotherapy-based therapies for bladder cancer. Impact: Our highly complementary group of accomplished investigators bring to bear longstanding expertise and translational experience in EV biology, bioengineering, systems biology, bioinformatics, and clinical oncology. If successful, our urinary nanoplasmonic EV platform would add critical actionable insights into immunotherapy-based treatments of advanced bladder cancers with promise in other prevalent genitourinary cancers such as kidney and prostate.

挑战。一旦转移，100个病人中只有5个活到5年。免疫检查点