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Evaluation of an implantable microdevice for rapid cancer drug screening directly in T cell lymphoma patients

直接对 T 细胞淋巴瘤患者进行快速癌症药物筛选的可植入微装置的评估

基本信息

批准号：
10031400
负责人：
Cecilia Larocca
金额：
$ 75.95万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10031400
关键词：
Address Animal Model Antineoplastic Agents Apoptosis Automobile Driving Biological Markers Biopsy Breast Cancer Patient Cancer Patient Cancerous Cell Communication Cell model Cells Cessation of life Clinical Clinical Trials Combined Modality Therapy Cutaneous Cutaneous T-cell lymphoma Data Development Devices Dose Drug Screening Drug usage Evaluation Familiarity Freezing Future Genetic Genomics Goals Grain Heterogeneity Histologic Hour Human Image Immune Immunofluorescence Immunologic Immunophenotyping Immunotherapy Implant In Situ In Vitro Incidence Investigation Investigational Drugs Lesion Location Malignant - descriptor Malignant Neoplasms Measures Medical Methods Microscopic Molecular Molecular Abnormality Morbidity - disease rate Mus Mutation Needles New Agents Oncogenes Oncogenic Pathway interactions Patients Periodicity Peripheral Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Phenotype Pilot Projects Population Positioning Attribute Predictive Value Property Proteins Resistance Resolution Rice Risk Sampling Signal Transduction Signaling Protein Skin Specimen T-Cell Lymphoma T-Lymphocyte Testing Therapeutic Time Tissues base biomarker panel cancer therapy cancer type clinical development clinical predictors clinical trial enrollment clinically relevant combinatorial cost effective drug candidate drug development drug sensitivity drug testing effective therapy exome sequencing first-in-human genome sequencing genomic profiles implantation improved in vivo Model individual patient innovation malignant breast neoplasm microdevice millimeter mouse model neoplastic cell novel optimal treatments patient response potential biomarker precision medicine precision oncology predicting response predictive marker response response biomarker safety and feasibility screening senescence side effect skin lesion standard of care systemic toxicity tool treatment response treatment strategy tumor tumor microenvironment tumor-immune system interactions

项目摘要

Project Summary/Abstract: Advanced cutaneous T cell lymphoma (CTCL) and peripheral T cell lymphoma (PTCL) have very poor survival due to limited effective treatments. Three major obstacles have stalled drug development: 1) the low number of patients with each T-cell lymphoma (TCL) subtype, which limits sample availability and clinical trial enrollment; 2) genetic and tissue microenvironment variability across subtypes; and 3) a lack of cellular and animal models to test immunotherapies. Thus, there is a major scientific gap in the development of new treatments for TCL. Here, we propose the use of an innovative implantable microdevice (MD), smaller than a grain of rice, that is placed directly into a patient's cancerous lesion to screen drugs and to identify the most effective cancer drug to treat TCL on a personalized level. Our MD delivers up to 20 drugs of any class into non-overlapping regions of a tumor. It is delivered into the skin with a small needle and retrieved in 3 days by excising the device along with a few millimeters of surrounding cancer tissue with a standard skin biopsy tool. This device allows testing drugs directly inside the living tumor with microdoses, thereby avoiding the risk of systemic side effects. Drug sensitivity is determined by histologic assessment of the tumor surrounding the device. The MD and the method for processing and analyzing tissue has been validated across multiple cancer types in mouse models and is being evaluated in an ongoing pilot study in breast cancer. The specific aims of these studies will be to: i) determine the safety and feasibility of implanting and retrieving the MD in skin lesions of TCL; ii) assess local responsiveness of TCL to cancer treatments delivered via the MD through microscopic assessments using highly multiplexed cyclic immunofluorescence, a novel platform capable of characterizing subcellular changes in the native immune microenvironment following drug treatment with over 30 markers, and iii) correlate genetic abnormalities of TCL with drug response to identify potential biomarkers of response and to determine if the MD can be used to predict clinical response by correlating the local tissue response to drug with a patient's clinical response to the same drug when given systemically. We hypothesize that in situ tissue profiling of drugs in TCL can predict systemic responses to standard of care therapies and therefore can serve as a rapid screen for multiple investigational single or combination treatments. Additionally, genomic and immunophenotypic analysis of tumors may assist in identification of predictive biomarkers of treatment. The results of our studies will focus clinical trial efforts toward the most promising treatment strategies and usher in the era of precision medicine in TCL.

项目总结/文摘: