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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）

基本信息

批准号：
10686016
负责人：
Cesar M Castro
金额：
$ 43.35万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
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/10686016
关键词：
Acceleration Anatomy Bioinformatics Biological Assay Biological Markers Biological Specimen Banks Biology Biomedical Engineering Bladder Bladder Urothelium Cancer Detection Cancer Patient Cancer cell line Cells Charge Clinical Clinical Oncology Clinical Trials Collection Consensus Correlative Study Coupled 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 Membrane Messenger RNA Molecular Molecular Profiling Monitor Nanotechnology Neoplasm Metastasis Nucleic Acids Oncologist Patients Performance 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 X-Ray Computed Tomography biomarker panel cancer therapy cell bank clinical imaging clinical investigation commercialization effective therapy exosome expectation experience extracellular vesicles imaging modality improved innovation insight instrumentation liquid biopsy multidisciplinary nanoGold nanometer nanoplasmonic novel novel marker peripheral blood personalized immunotherapy plasmonics pre-clinical pressure prospective repository response sensor tool translational study treatment strategy tumor tumor microenvironment tumor-immune system interactions urinary

项目摘要

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