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Nanoparticles to Track T Cell Immunotherapy Using Magnetic Particle Imaging

使用磁粒子成像追踪 T 细胞免疫治疗的纳米粒子

基本信息

批准号：
10365339
负责人：
Carlos M Rinaldi-Ramos
金额：
$ 47.21万
依托单位：
UNIVERSITY OF FLORIDA
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：
2022-05-15 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10365339
关键词：
Adoptive Cell Transfers Affect Animals Anisotropy Benchmarking Biodistribution Biological Assay Biomedical Engineering Blood Circulation Time Caliber Cancer Model Cell Count Cell Survival Cells Charge Coculture Techniques Computer Models Coupled Cytotoxic T-Lymphocytes Defect Disease Dose Electron Microscopy Environment Euthanasia Exocytosis Failure Flow Cytometry Fluorescence Microscopy Foundations Future Generations Glioblastoma Glioma Goals Image Imaging technology Immunotherapy Impact evaluation In Vitro Intracranial Neoplasms Ionizing radiation Label Life Longitudinal Studies Magnetic Resonance Imaging Magnetic nanoparticles Magnetism Malignant Neoplasms Measures Mediating Methods Modeling Modification Molecular Monitor Motivation Multimodal Imaging Mus Organ Oxygen Penetration Performance Phenotype Physics Polymers Preclinical Testing Property Quantitative Evaluations Research Research Project Grants Resolution Route Signal Transduction Site Solid Solid Neoplasm Specificity Stratification Surface T cell therapy T-Lymphocyte Therapeutic Tissues Toxic effect Tracer Validation Work biomaterial development cancer cell cancer immunotherapy cancer therapy clinical translation cytotoxic imaging approach imaging modality immune imaging improved in vivo insight instrumentation interest iron oxide nanoparticle magnetic field melanoma molecular imaging mouse model nanoparticle neoplastic cell nuclear imaging particle preclinical evaluation public health relevance quantitative imaging research and development responders and non-responders response success superparamagnetism tomography tool trafficking treatment response tumor uptake

项目摘要

Project Summary A critical step in the success of adoptive cell transfer (ACT) T cell immunotherapy in solid cancers is achieving trafficking and persistence of T cells at tumor sites, while avoiding toxicities due to T cell attack of off-target tissues and organs. Non-invasive quantitative imaging would be a powerful tool to understand mechanisms of action and failure of T cell immunotherapies, evaluate the impact of T cell modifications and delivery routes, monitor off-target T cell accumulation, and stratify response to therapy on the basis of measures of T cell tumor accumulation. This Bioengineering Research Grant project will pioneer non-invasive and quantitative tracking of adoptive T cell cancer immunotherapy using magnetic particle imaging (MPI), a new molecular imaging modality that enables non-invasive, unambiguous, and tomographic analysis of the whole-body distribution of superparamagnetic iron oxide nanoparticles (SPIONs). Preliminary results demonstrate non-invasive quantitative tracking of ACT T cells in solid intracranial tumors, synthesis of tracers with enhanced MPI sensitivity, and current sensitivity of 5x103 T cells. The proposed work aims to improve sensitivity to 5x102 T cells and demonstrate the accuracy of MPI in quantifying T cell biodistribution in mouse models of cancer. Modeling of MPI physics by the PI demonstrates that tracers optimal for MPI must have uniform physical and magnetic properties and low magnetocrystalline anisotropy, to enable fast dipole switching at large SPION diameters. The PI has developed a new synthesis that yields defect-free SPIONs with uniform magnetic properties and low magnetocrystalline anisotropy. The proposed work (Aim 1) will couple this new synthesis with modeling of MPI physics and comprehensive physical and magnetic characterization to gain fundamental understanding of the relation between SPION properties and MPI performance and to obtain SPIONs with superior sensitivity. Imaging approaches to track T cells must not compromise their viability or function and T cells pose unique challenges for nanoparticle labeling. The proposed work (Aim 2) will define an upper limit for labeling primary T cells with MPI tracers without compromising viability or function using tracers that associate with T cells through charge interactions. Preliminary studies demonstrate non-invasive tracking of T cell biodistribution in mice using MPI, and that SPION-labeled T cells reach solid tumors after systemic administration in murine models. The proposed work (Aim 3) will validate in vivo tracking of ACT T cell therapy using MPI against T cell counting using flow cytometry and will evaluate dynamics of T cell accumulation in tumors longitudinally using MPI. The proposed biomaterials-development research plan is enabled by the complementary expertise of the PI (SPIONs and MPI physics) and Co-I (ACT T cell therapies) and access to state-of-the-art instrumentation to characterize SPION MPI performance ex vivo and in vivo. Achieving the target sensitivity of 5x102 T cells will provide an order-of- magnitude improvement in quantitative cell tracking sensitivity over other whole body quantitative imaging technologies, establishing MPI as a powerful tool in the immunoimaging toolbox.

项目总结