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Validation of a novel 3D culture platform for TNBC treatment selection

验证用于 TNBC 治疗选择的新型 3D 培养平台

基本信息

批准号：
10540094
负责人：
David Gallup
金额：
$ 64.42万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10540094
关键词：
3-Dimensional Address Adriamycin PFS Architecture Biological Assay Biotechnology Breast Cancer Patient Breast Cancer Treatment Businesses Cancer Center Cancer Diagnostics Cancer Patient Carboplatin Cells Cessation of life Characteristics Chemicals Clinical Clinical Data Clinical Research Clinical Trials Cyclophosphamide Data Diagnostic tests Doxorubicin Engineering Evaluation Genomics Goals Immuno-Chemotherapy Immunotherapy Individual Industrialization Legal patent Malignant Neoplasms Measures Mechanics Methodist Church Methods Modeling Molecular Profiling Mutation Neoadjuvant Therapy Oncology Organoids Outcome Paclitaxel Patient Care Patient Care Team Patient-derived xenograft models of breast cancer Patients Pharmaceutical Preparations Physicians Prospective Studies Reagent Reporting Research Research Institute Resolution Retrospective Studies Scientist Selection for Treatments Serum Slice Solid Solid Neoplasm System T-Cell Activation Testing Time Tissues Translating Tumor Biology Tumor Tissue Validation anti-PD-L1 anti-PD-L1 therapy anticancer research base cancer care cancer diagnosis chemotherapy clinical care clinical practice clinical translation clinically actionable cost design diagnostic assay drug sensitivity evidence base genomic profiles improved in vivo individual patient malignant breast neoplasm metastatic colorectal mouse model novel patient derived xenograft model patient response pembrolizumab personalized care personalized medicine precision drugs precision medicine product development prospective resistance mechanism responders and non-responders response standard of care targeted treatment taxane three dimensional cell culture tissue culture treatment response treatment strategy triple-negative invasive breast carcinoma tumor tumor immunology tumor microenvironment

项目摘要

PROJECT SUMMARY The goal of this academic [Houston Methodist Research Institute (HMRI) and MD Anderson Cancer Center (MDACC)] and industrial (EMPIRI) collaborative project is to validate a novel, functional cancer diagnostic assay for clinical translation to improve and personalize the care of triple-negative breast cancer (TNBC) patients. The study will validate a novel 3D tumor tissue culture method (E-slices) invented by MPI Kyuson Yun (HMRI) and licensed to EMPIRI, Inc., a biotech startup co-founded by Dr. Yun and Dave Gallup (MPI). Together with Dr. Naoto Ueno (MPI, MDACC), a renowned physician-scientist specializing in TNBC research and patient care, the team will validate the predictive accuracy of E-slices for individual TNBC patient responses to recently approved chemoimmunotherapy for early TNBC patient care. The need for personalized medicine in oncology is widely accepted but translating this important concept into clinical practice has been challenging. Currently, the dominant platform for precision medicine utilizes genomics/sequencing-based assays to measure the expression and/or mutational profiles and then infer responses to targeted therapies; however, this approach benefits <10% of patients with profiled tumors. Recognizing the inherent limitations of these inference-based methods, functional assays (e.g., organoids, PDX models) have been developed, but these approaches have numerous limitations including high cost and time required to establish the models, low “take rates”, and destruction of the native tumor microenvironment (TME). To overcome these challenges, EMPIRI developed a novel 3D ex vivo tumor culture method (E-slices) that enables rapid, personalized drug sensitivity testing in intact patient tumor tissues. E-slices retain the native TME and tissue architecture and are cultured in serum-free defined media, overcoming the limitations of other approaches. In addition, E-slices can be generated from any solid tumor and used for testing responses to chemotherapy, targeted therapy, and immunotherapy. Importantly, E-slice accuracy has been validated in a clinical setting for metastatic colorectal cancer to accurately predict individual patient treatment responses and detect inter-patient differences to the same treatments in 4-12 days, paving the way for near evidence-based personalized treatment selections. The team will: (i) determine whether E-slices predict patient responses to SOC NAC: doxorubicin (Adriamycin) plus cyclophosphamide) in a retrospective study, (ii) measure chemoimmunotherapy (Pembrolizumab plus paclitaxel + carboplatin) responses in humanized PDX slices from known responders and non-responders; and (ii) evaluate the clinical utility of E-slices in predicting TNBC patient responses to newly approved standard of care chemoimmunotherapy in a prospective study. Successful completion of this project will provide the necessary data to apply E-slices as the first functional cancer diagnostic test specifically designed to inform TNBC patient care.

项目总结