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:
- 金额:$ 64.42万
- 依托单位:
- 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:
- 关键词:3-DimensionalAddressAdriamycin PFSArchitectureBiological AssayBiotechnologyBreast Cancer PatientBreast Cancer TreatmentBusinessesCancer CenterCancer DiagnosticsCancer PatientCarboplatinCellsCessation of lifeCharacteristicsChemicalsClinicalClinical DataClinical ResearchClinical TrialsCyclophosphamideDataDiagnostic testsDoxorubicinEngineeringEvaluationGenomicsGoalsImmuno-ChemotherapyImmunotherapyIndividualIndustrializationLegal patentMalignant NeoplasmsMeasuresMechanicsMethodist ChurchMethodsModelingMolecular ProfilingMutationNeoadjuvant TherapyOncologyOrganoidsOutcomePaclitaxelPatient CarePatient Care TeamPatient-derived xenograft models of breast cancerPatientsPharmaceutical PreparationsPhysiciansProspective StudiesReagentReportingResearchResearch InstituteResolutionRetrospective StudiesScientistSelection for TreatmentsSerumSliceSolidSolid NeoplasmSystemT-Cell ActivationTestingTimeTissuesTranslatingTumor BiologyTumor TissueValidationanti-PD-L1anti-PD-L1 therapyanticancer researchbasecancer carecancer diagnosischemotherapyclinical careclinical practiceclinical translationclinically actionablecostdesigndiagnostic assaydrug sensitivityevidence basegenomic profilesimprovedin vivoindividual patientmalignant breast neoplasmmetastatic colorectalmouse modelnovelpatient derived xenograft modelpatient responsepembrolizumabpersonalized carepersonalized medicineprecision drugsprecision medicineproduct developmentprospectiveresistance mechanismresponders and non-respondersresponsestandard of caretargeted treatmenttaxanethree dimensional cell culturetissue culturetreatment responsetreatment strategytriple-negative invasive breast carcinomatumortumor immunologytumor 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
这位学者的目标是[休斯顿卫理公会研究院(HMRI)和MD安德森癌症
中心(MDACC)]和工业(EMPIRI)的合作项目是验证一种新的功能性癌症
用于临床翻译的诊断分析,以改进和个性化三阴性乳腺癌的护理
(TNBC)患者。这项研究将验证MPI发明的一种新的三维肿瘤组织培养方法(E-Slice
Kyuson Yun(HMRI),并授权给EMPIRI,Inc.,一家由Yun博士和戴夫·盖洛普共同创立的生物技术初创公司
(MPI)。与专门研究TNBC的著名内科科学家上野直人博士(MPI,MDACC)一起
研究和患者护理,团队将验证E-Slice对个别TNBC患者的预测准确性
对新近批准的用于早期TNBC患者护理的化学免疫疗法的反应。
肿瘤学对个性化医学的需求被广泛接受,但将这一重要概念
进入临床实践一直是具有挑战性的。目前,精准医疗的主导平台利用
基于基因组学/测序的分析,以测量表达和/或突变图谱,然后推断
对靶向治疗的反应;然而,这种方法使10%的横断面肿瘤患者受益。
认识到这些基于推理的方法的固有局限性,功能分析(如有机物、PDX
模型),但是这些方法有许多限制,包括高成本和高时间
需要建立模型,低的“采用率”,以及自然肿瘤微环境(TME)的破坏。
为了克服这些挑战,EMPIRI开发了一种新的3D体外肿瘤培养方法(E-Slice)
这使得在完整的患者肿瘤组织中进行快速、个性化的药物敏感性测试成为可能。电子切片保留了
原生TME和组织结构,并在无血清定义的培养基中培养,克服了
其他方法。此外,E切片可以从任何实体肿瘤中产生,并用于测试对
化疗、靶向治疗和免疫治疗。重要的是,E-Slice的准确性已经在
转移性结直肠癌的临床环境以准确预测个体患者的治疗反应和
在4-12天内检测相同治疗的患者间差异,为近乎循证的治疗铺平道路
个性化的治疗选择。该团队将:(I)确定E-Slice是否可以预测患者对
SOC NAC:阿霉素(阿霉素+环磷酰胺)在一项回顾性研究中,(Ii)测量
人源化PDX切片的化学免疫治疗(培溴利珠单抗+紫杉醇+卡铂)反应
已知的应答者和无应答者;以及(Ii)评估E-切片在预测TNBC患者中的临床应用
一项前瞻性研究对新批准的护理标准化疗免疫疗法的反应。成功
该项目的完成将为应用E-Slice作为第一个功能性癌症诊断提供必要的数据
专门为告知TNBC患者护理而设计的测试。
项目成果
期刊论文数量(0)
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David Gallup其他文献
David Gallup的其他文献
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{{ truncateString('David Gallup', 18)}}的其他基金
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
- 批准号:
10707311 - 财政年份:2022
- 资助金额:
$ 64.42万 - 项目类别:
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