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Oncophysics核心 - 摘要 最近已证明癌症免疫疗法对治疗肺癌非常有效 和黑色素瘤，但对于包括乳腺和胰腺癌在内的其他适应症，其应用仍然是 考虑到后来的癌症提出的其他挑战（低免疫原性）。我们相信 全身和在肿瘤中优化药物和免疫细胞的运输和穿透 微环境将改善这些癌症的免疫反应。那，运输的影响 免疫治疗效率的现象（肿瘤的物理时空参数和肿瘤畸变） 应考虑开发有效的免疫疗法。提议的中心 免疫治疗转运肿瘤物质（CITO）着重于确定这些转运现象 在乳腺癌和胰腺肿瘤模型中，为了改善免疫疗法的运输 最终，作为患者的最佳免疫治疗方案的合理设计 个性化疗法。支持CITO及其2个研究项目[癌症运输项目1 纳米树突（DC）疫苗；肿瘤微环境中生物物理屏障的项目2]， 运输肿瘤物理核心（TOC）将提供成像，分析，定量和独特的肿瘤物理 基于肿瘤物理建模 框架运输和生物分布理论（TBT）。 TBT从经典工具中移动边界 研究药代动力学和有效关系，而是创建新颖的精确免疫治疗工具 合理地为患者量身定制个人治疗。 TOC的总体假设是生物物理 组织的特性（作为生物屏障）是决定生物分布的确定性 免疫治疗药，上游（但与特定的）特定生物靶标的识别。分布 影响有效性，不良反应和抵抗现象，并最终 - 患者结果。 TOC会 从两个项目中汇总数据，然后提供特定的服务以合理化的发展和 改善免疫治疗药的递送。 TOC将为项目提供三个主要服务：成像 （PET，IVM），数据分析和定量以及计算生物分布和肿瘤生长的应用 型号。基本的逻辑是，体内和病理成像提供了快照和时间范围 理论的生物分布。单个时间点和运输动力的数量将创造 计算模型的数据时间序列，以开发时空生物分布，这是 肿瘤微环境，免疫治疗方式及其在治疗上的运输特性 相关的时间表。免疫疗法剂的生物分布和控制运输的调节器的影响 免疫疗法将与治疗结果和肿瘤生长相关。