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

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

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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.

项目摘要这个学术[休斯顿卫理公会研究所（HMRI）和MD Anderson Cancer的目标中心（MDACC）]和工业（Empiri）协作项目是验证一种新型的功能性癌症临床翻译的诊断测定法改善和个性化三阴性乳腺癌的护理（TNBC）患者。该研究将验证MPI发明的新型3D肿瘤组织培养法（E-SINITES） Kyoson Yun（HMRI），并获得了由Yun博士和Dave Gallup共同创建的生物技术初创公司的Empiri，Inc。（MPI）。与Naoto Ueno博士（MPI，MDACC）一起，专门从事TNBC的著名身体科学家研究和患者护理，团队将验证单个TNBC患者电子分段的预测准确性对最近批准的TNBC患者护理的化学免疫性疗法的反应。肿瘤学中对个性化医学的需求已被广泛接受，但翻译了这一重要概念进入临床实践已受到挑战。目前，精密医学的主要平台使用基于基因组学/测序的测定法，以测量表达和/或突变特征，然后影响对目标疗法的反应；但是，这种方法受益于<10％的分类肿瘤患者。识别这些基于推断的方法的继承局限性，功能分析（例如，器官，PDX 已经开发了模型），但是这些方法有许多限制，包括高成本和时间建立模型，较低的“率”以及对天然肿瘤微环境（TME）的破坏所需的要求。为了克服这些挑战，Empiri开发了一种新型的3D离体肿瘤培养方法（E分裂）这样可以在完整的患者肿瘤组织中快速，个性化的药物敏感性测试。电子单位保留天然TME和组织结构，并在无血清定义培养基中进行培养，克服了局限性其他方法。此外，可以从任何实体瘤生成电子分段，并用于测试对化学疗法，靶向治疗和免疫疗法。重要的是，电子滑板的准确性已在A中验证转移性结直肠癌的临床环境，以准确预测单个患者治疗反应和在4-12天内检测患者间差异与同一治疗的差异，为近证据铺平了道路个性化治疗选择。团队将：（i）确定电子单位是否预测患者对 SOC NAC：阿霉素（阿霉素）加环磷酰胺）在回顾性研究中，（ii）测量人源化PDX切片中的化学免疫疗法（Pembrolizumab加紫杉醇 +紫杉醇）反应已知的响应者和非反应者；（ii）评估电子切片在预测TNBC患者中的临床实用性在一项前瞻性研究中，对新认可的护理化学免疫疗法的反应。成功的该项目的完成将提供必要的数据，以将电子切片作为第一个功能性癌症诊断专门设计的测试旨在为TNBC患者护理提供信息。