Gene Therapy for Brain Tumors

脑肿瘤的基因治疗

基本信息

批准号：
7596613
负责人：
FRED H HOCHBERG
金额：
$ 4.14万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-08-15 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7596613
关键词：
Address Adjuvant Chemotherapy Adoption Adult Glioma Alkylating Agents American Anaplastic astrocytoma Animal Model Antigens Apoptosis Appearance Area Astrocytes Astrocytoma Back Benign Binding Biologic Development Biological Markers Biological Response Modifier Therapy Biology Blood - brain barrier anatomy Brain Neoplasms Callithrix Cancer Therapy Evaluation Program Caring Carmustine Cell Differentiation process Cell Therapy Cells Cellular biology Chemicals Clinic Clinical Clinical Sciences Clinical Trials Cognitive Collaborations Complementary therapies Complex Cyclophosphamide Cytotoxic T-Lymphocytes Development Diagnosis Dose Drug Delivery Systems Drug Formulations Drug Industry Effectiveness Elements Emotional End Point Endopeptidases Engineering Environment Epidermal Growth Factor Receptor Event Excision Failure Family member Funding Future Gene Transduction Agent Genes Genetic Genetic Heterogeneity Gliadel Glioblastoma Glioma Goals Guanosine Monophosphate HSV-1 vector Histologic Histopathologic Grade Human Image Imaging Device Immune response Immunologic Receptors Infectious Agent Institution Invasive Investigational Therapies Label Lead Left Lesion Leucocytic infiltrate Malignant - descriptor Malignant Glioma Malignant Neoplasms Mean Survival Times Modality Modeling Molecular Molecular Target Molecular Virology Monitor Mutation Natural Immunity Neoplasms Neurons Neurosciences New Approaches to Brain Tumor Therapy Consortium Nitrosourea Compounds Nuclear Pore Complex Numbers Oligonucleotide Microarrays Oncolytic Oncolytic viruses Operative Surgical Procedures Orphan Outcome PTEN gene Paralysed Pathologic Pathway interactions Patients Peptide Hydrolases Peptides Perception Pharmaceutical Preparations Phase Phase I Clinical Trials Physiological Process Prodrugs Production Productivity Protein p53 Protocols documentation Radiation Radiation therapy Radiosurgery Recording of previous events Recurrence Relative (related person)Research Research Personnel Resistance Resources Risk Rodent Safety Solid Specificity Staging Stem cells T-Cell Receptor T-Lymphocyte Testing Therapeutic Therapeutic Intervention Thinking Time Toxic effect Transgenes Translating Translations Tropism Tumor Suppressor Proteins Tumor Tissue United States Food and Drug Administration Upper arm Vacuum Viral Viral Genes Virus Week World Health Organization adeno-associated viral vector base brain cell cell killing combinatorial concept cost drug development epidermal growth factor receptor VIII gene therapy improved in vivo killings molecular imaging mutant neoplastic cell nerve stem cell neuro-oncology novel oncolysis oncolytic vector pre-clinical precursor cell programs relating to nervous system success targeted delivery tumor vector

项目摘要

Malignant gliomas represent the single most costly and morbid neoplasm per capita. During previously funded years,this Program Project has evaluated a pipeline of potential biologic therapies of this tumor. We now propose to manufacture and translate one therapy, an oncolytic HSV-1 vector ("MGH-2"), which activates prodrugs, into three clinical phase I trials. At the same time this project proposes to continue to develop additional tumor-targetting therapies, novel imaging tools and to understand mechanisms of potential resistance. Four projects and three Cores are united in collaboration with GMP-production facilities of Dr. Glorioso, as a resource for the brain-tumor consortium (NABTT) to explore gene therapy for glioblastomas. Project 1 (Chiocca) will determine mechanisms of the host response to the oncolytic virus and how this host response can be modulated to provide more efficient tumor killing . Project 4 (Breakefield/Sena-Esteves) will enhance tumor targeting by HSV-1 vectors specifically directed against mutant EGFr in combination with Neural Precursor cells to protect normal brain from tumor recurrence. Project 2 (Carter) will develop a complementary cellular therapeutic strategy to target human T lymphocytes to intracranial glioblastomas by genetically engineering them to express chimeric immune receptors which recognize antigens identified in Projects I and 3. Project 3 (Weissleder ) will identify peptides which selectively label and image therapeutic NPC and T cells and oncolytic viruses in glial tumors, and correlate novel imaging modalities with the biologic therapies explored in Projects 1,2 and 4.Clinical Core B (Hochberg/Glorioso/Tufaro) will pilot the production of MGH-2 and create sufficient GMP product to perform the three phase I trials. The Core will generate the FNDs and trial protocols as well as toxicity and human efficacy endpoints in support of all trials at both the MGH and OSU institutions. The vector will be offered to CTEP for phase II NABTT trials. . Human and rodent and pre-clinical marmoset studies will be supported by statistical oversight (Dr. Finkelstein) and histologic, molecular pathologic and immunocytochemical evalutions of brain tumor tissue (Core C, Louis). This program defines rational and scientific means to evaluate and expand the potential of gene therapy for brain tumors.