Transport Oncophysics Core

运输肿瘤物理学核心

• 批准号: 9752962
• 负责人: Haifa Shen
• 金额: $ 38.95万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9752962
• 关键词: Adjuvant; Adverse effects; Affect; Biodistribution; Biological; Biological Transport; Biophysics; Cells; Clinical; Communities; Computer Simulation; Data; Data Aggregation; Data Analyses; Data Set; Development; Dimensions; Disease; Drug Kinetics; Drug Transport; Education and Outreach; Educational Models; Funding; Goals; Heterogeneity; Image; Image Analysis; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; Individual; Kinetics; Knowledge; Laws; Link; Logic; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Mammary Neoplasms; Modality; Modeling; Patient-Focused Outcomes; Patients; Penetration; Performance; Pharmaceutical Preparations; Physics; Positron-Emission Tomography; Process; Property; Rationalization; Regimen; Research; Research Personnel; Research Project Grants; Resistance; Role; Series; Services; Therapeutic; Therapeutic Agents; Time; Tissues; Treatment Efficacy; Vaccines; base; biophysical properties; cancer immunotherapy; computerized tools; data integration; data management; data sharing; data warehouse; design; effective therapy; expiration; immunogenicity; improved; in vivo; individualized medicine; innovation; intravital microscopy; malignant breast neoplasm; melanoma; nano; nanovaccine; neglect; novel; novel therapeutics; oncology; outreach program; pancreatic cancer model; pancreatic neoplasm; pathology imaging; physical science; spatiotemporal; synergism; theories; therapy outcome; therapy resistant; tool; tumor; tumor growth; tumor microenvironment

TRANSPORT ONCOPHYSICS CORE – SUMMARY Cancer immunotherapy has recently been demonstrated to be quite effective for the treatment of lung cancer and melanoma, but for other indications including breast and pancreatic cancers, its application remains to be determined, given the additional challenges posed by the latter cancers (low immunogenicity). We believe that optimizing the transport and penetration of drugs and immune cells, systemically and in the tumor microenvironment, would improve the immune response in these cancers. Thus, the impact of transport phenomena (physical spatio-temporal parameters and aberrations of tumors) on immunotherapeutic efficacy should be considered for the development of effective immunotherapies. The proposed Center for Immunotherapeutic Transport Oncophysics (CITO) is focused on determining these transport phenomena in breast and pancreatic tumor models, in order to improve the transport of immunotherapies through tissues and, ultimately, to enable the rational design of optimal immunotherapeutic regimens for patients as part of individualized therapy. To support the CITO and its 2 research projects [Project 1 for the transport of cancer Nano-dendritic (DC) vaccines; Project 2 for the biophysical barriers in the tumor microenvironment], the Transport Oncophysics Core (TOC) will provide imaging, analysis, quantification, and unique oncophysical computational tools to rationalize the delivery of immunotherapies, based on the oncophysical modeling framework Transport and Biodistribution Theory (TBT). The TBT moves boundaries from classical tools used to study pharmacokinetic and efficacy relations, and instead creates novel precision immunotherapeutic tools to rationally tailor individual treatments to patients. The overall hypothesis of the TOC is that the biophysical properties of tissues (as biological barriers) are determinants that govern biodistribution of immunotherapeutics, upstream of (but in synergy with) specific biological target recognition. The distribution affects efficacy, adverse effects, and resistance phenomena, and, ultimately - patient outcomes. The TOC will aggregate data from the two projects and then provide specific services to rationalize development of and to improve the delivery of immunotherapeutics. The TOC will offer three major services to the projects: imaging (PET, IVM), data analysis and quantification, and application of computational biodistribution and tumor growth models. The underlying logic is that in vivo and pathology imaging provides snapshots and time-lapses of the biodistribution of therapeutics. The quantification of individual time-points and transport dynamics will create time series of data for computational models to develop spatio-temporal biodistribution, which is a function of the tumor microenvironment, immunotherapeutic modality, and their transport properties at therapeutically relevant time-scales. Biodistribution of immunotherapy agents and the effects of adjuvants controlling transport of immunotherapies will be correlated to therapeutic outcomes and tumor growth.

运输肿瘤物理学核心 – 摘要 癌症免疫疗法最近被证明对治疗肺癌相当有效 和黑色素瘤，但对于包括乳腺癌和胰腺癌在内的其他适应症，其应用仍有待确定 考虑到后一种癌症带来的额外挑战（低免疫原性），我们确定了这一点。 优化药物和免疫细胞的全身和肿瘤中的运输和渗透 微环境将改善这些癌症的免疫反应，从而改善运输的影响。 现象（物理时空参数和肿瘤畸变）对免疫治疗效果的影响 应考虑开发有效的免疫疗法。 免疫治疗转运肿瘤物理学 (CITO) 专注于确定这些转运现象 在乳腺癌和胰腺肿瘤模型中，以改善免疫疗法在组织中的转运 并最终为患者提供最佳合理的免疫治疗方案设计，作为 支持 CITO 及其 2 个研究项目 [项目 1：癌症转移] 纳米树突（DC）疫苗；肿瘤微环境中的生物物理屏障项目2] 运输肿瘤物理学核心（TOC）将提供成像、分析、量化和独特的肿瘤物理学 基于肿瘤物理模型的计算工具，使免疫疗法的实施合理化 运输和生物分布理论 (TBT) 框架 TBT 突破了所使用的经典工具的界限。 研究药代动力学和功效关系，并创建新型精准免疫治疗工具 TOC 的总体假设是生物物理学。 组织的特性（作为生物屏障）是控制生物分布的决定因素 免疫治疗，特定生物靶标识别的上游（但与之协同）。 TOC 会影响疗效、不良反应和耐药现象，并最终影响患者的治疗结果。 汇总两个项目的数据，然后提供具体服务以合理化开发并 TOC 将为这些项目提供三项主要服务：成像。 （PET、IVM）、数据分析和量化以及计算生物分布和肿瘤生长的应用 模型的基本逻辑是体内和病理成像提供快照和延时。 治疗药物的生物分布的量化将产生个体时间点和运输动力学。 用于开发时空生物分布的计算模型的时间序列数据，它是以下函数 肿瘤微环境、免疫治疗方式及其传输特性 免疫治疗药物的生物分布和控制转运的佐剂的作用。 免疫疗法的效果将与治疗结果和肿瘤生长相关。