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Design of a Novel Nanocarrier Technology to Drug-Load CAR T cells

用于载药 CAR T 细胞的新型纳米载体技术的设计

基本信息

批准号：
10734365
负责人：
David Akhavan
金额：
$ 57.44万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734365
关键词：
Address Adjuvant Adoptive Cell Transfers Adult Affect Antibody Specificity Biochemical Brain Neoplasms Cell Survival Cell physiology Cells Cessation of life Chimeric Proteins Clinical Clinical Trials Cytolysis Data Disease Doctor of Philosophy Dominant-Negative Mutation Drug Utilization Drug toxicity Drug vehicle Epidermal Growth Factor Receptor Esters Evaluation Excision FDA approved Gingiva Glioblastoma Goals Growth Factor Inhibition Growth Factor Receptors Half-Life Hematologic Neoplasms Hemorrhage Histiocytosis Immune In Vitro Intracranial Hemorrhages Kansas Label Laboratories Life Macrophage Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of prostate Mediating Modeling Mus Nanotechnology Oncogenic Patients Penetration Peptides Pharmaceutical Preparations Phosphotransferases Polymers Pre-Clinical Model Principal Investigator Production Recurrence Reporting Research Resistance Route Solid Neoplasm T cell therapy T-Lymphocyte Technology Testing Therapeutic Toxic effect Transforming Growth Factors Universities Up-Regulation cell killing chemoradiation chimeric antigen receptor chimeric antigen receptor T cells comparative efficacy cytokine design dosage drug candidate experience immunotoxicity improved in vivo inhibitor interest invention kinase inhibitor manufacture nanocarrier nanotechnology platform new therapeutic target novel novel therapeutics overexpression pre-clinical programmed cell death ligand 1 receptor research clinical testing response small molecule small molecule inhibitor success systemic toxicity targeted treatment technology platform therapeutic target tumor tumor eradication tumor microenvironment tumor specificity uptake

项目摘要

Project summary: Current treatment for Glioblastoma Multiforme (GBM), the most common malignant brain tumor in adults, involves maximal safe resection, followed by adjuvant chemoradiation. Although this treatment is life prolonging, it is never curative. Five year survival is less than 7 %1 and improved therapies are urgently needed. In this proposal, we aim to develop a new targeted therapy with reduced toxicity and increased efficacy for GBM patients by leveraging nanotechnology discoveries in our laboratory to improve adoptive cell therapy. Chimeric Antigen Receptor (CAR) T cells combine the cytolytic potency of a T cell with the tumor specificity of an antibody. Recent clinical trial experiences of CAR T cells in solid tumors have identified the immune-suppressive tumor microenvironment (TME) as a major barrier to clinical success2-4. One immune-suppressive endogenous negative regulator in GBM TME is TGFβ, which has been identified as barrier to CAR T tumor eradication. Small molecule inhibitors of the TGFβ receptor as well as TGFβ resistant CAR T cells have been developed and tested clinically, however they are limited due to systemic toxicity. Herein we propose developing a platform technology to drug-load CAR T cells with nanocarriers, thus enhancing the therapeutic window of CAR T cells, and addressing one of the major obstacles to CAR T cells in brain tumors.

项目总结: