Center for Immunotherapeutic Transport Oncophysics

免疫治疗运输肿瘤物理学中心

• 批准号: 9752959
• 负责人: JENNY C-N CHANG
• 金额: $ 163.83万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-29 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752959
• 关键词: Address; Adjuvant; Affect; Animal Model; Area; Biodistribution; Biological; Biomimetics; Biophysics; Blood Vessels; Cancer Biology; Cancer Immunology Science; Cells; Chemistry; Clinical; Clinical Oncology; Code; Coupling; Cues; Dendritic Cell Vaccine; Development; Diagnostic; Disseminated Malignant Neoplasm; Drug Delivery Systems; Drug Kinetics; Education and Outreach; Engineering; Evolution; Foundations; Funding; Genetic Engineering; Goals; Image; Imaging technology; Immune; Immunology; Immunotherapeutic agent; Immunotherapy; Infiltration; Institution; Knowledge; Lymphatic; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Mammary Neoplasms; Mathematics; Medical; Medical center; Metastatic Melanoma; Methodist Church; Modeling; Mus; Pathology; Patient Selection; Phenotype; Physics; Process; Property; Protocols documentation; Research; Research Institute; Research Personnel; Research Project Grants; Resistance; Resource Sharing; Resources; Silicon; Technology; Texas; Therapeutic; Therapeutic Agents; Treatment Efficacy; Tropism; United States Food and Drug Administration; Universities; University of Texas M D Anderson Cancer Center; Vaccines; Work; anticancer activity; base; cancer imaging; cancer type; computer framework; computer science; computerized tools; design; imaging modality; immunogenicity; improved; in vivo imaging; innovation; malignant breast neoplasm; nano; nanotherapeutic; novel; novel therapeutics; oncology; pancreatic neoplasm; personalized immunotherapy; personalized medicine; personalized therapeutic; physical science; programs; spatiotemporal; success; theories; therapeutic target; therapy resistant; tumor; tumor growth; tumor microenvironment; tumor progression

OVERALL – SUMMARY The US Food and Drug Administration recently approved several immunotherapies for the treatment of metastatic melanoma and lung cancer, based on their robust anti-cancer activities. Intense effort to apply immunotherapies for many other cancers, including breast and pancreatic cancers, have not yet met with similar success. Much of the effort has been focused on the study of the biological aspects of different immunotherapeutics, rather than the physical spatio-temporal peculiarities and aberrations of tumors (e.g., poor lymphocyte infiltration), which we believe are key parameters for improving the efficacy of immunotherapies. Recent evidence emphasizes the importance of processes within the tumor microenvironment over systemic pharmacokinetics for therapeutic efficacy. Thus, the impact of transport phenomena on immunotherapeutic efficacy (and therapeutic resistance) should be considered when developing strategies for new immunotherapies. Within this conceptual framework, the proposed Center for Immunotherapeutic Transport Oncophysics (CITO) focuses on: 1) understanding transport limitations of immune cells and immunotherapeutics; 2) establishing a precision immunotherapeutics framework on the basis of transport oncophysics; and 3) exploiting oncophysical transport-based cues for the development of successful personalized immunotherapeutics strategies based on transport phenotypes. Our overarching strategy comprise many innovations, including transport as a resistance for immunotherapies, nanotherapeutic vaccines, biomimetic constructs, precision immunotherapeutics, biodistribution theory, and oncophysics models for transport, biodistribution and tumor growth. The research projects focus on breast and pancreatic cancers, as those are cancer types with significant clinical challenges. In particular, we will determine the transport of Nano-DC vaccines and immune cells, and how they can be modulated to affect immunogenicity and therapeutic efficacy, with primary focus on breast cancer (Project 1). We will also determine the biophysical transport barrier(s) within the pancreatic cancer tumor microenvironment that can be modulated to affect the efficacy of immunotherapies (Project 2). Both projects focus on immune cell transport across many transport-limiting barriers (e.g., lymphatics, stroma, and vascular leakiness). They also share a set of animal models, therapeutic, and adjuvant agents, and they are also supported by the Transport Oncophysics Core (TOC). The CITO's overall objectives for the proposed funding period are: 1) to determine transport properties of immunotherapeutic agents in breast and pancreatic tumors; 2) to establish a predictive computational transport oncophysics framework for cancer immunotherapeutics; 3) to determine the extent of therapeutic resistance caused by therapeutic transport limitations and their evolution during cancer progression; and 4) to optimize and personalize systemic immunotherapeutic strategies based on the results of the first three objectives.

总体 - 摘要 美国食品药品监督管理局最近批准了几种治疗的免疫疗法 基于其强大的抗癌活性，转移性黑色素瘤和肺癌。激烈的申请努力 许多其他癌症的免疫疗法，包括乳腺癌和胰腺癌，尚未遇到 类似的成功。大部分努力都集中在研究不同的生物学方面 免疫治疗药，而不是肿瘤的物理时空特性和畸变（例如， 淋巴细胞浸润差），我们认为这是提高效率的关键参数 免疫疗法。最近的证据强调了肿瘤过程中过程的重要性 在全身药代动力学上的微环境以用于治疗效率。那，运输的影响 当免疫治疗效率（和治疗性抗性）上的现象应考虑 制定新免疫疗法的策略。在这个概念框架内，提议的 免疫治疗运输肿瘤物（CITO）重点是：1）了解运输限制 免疫细胞和免疫治疗药； 2）建立精确的免疫治疗框架 运输肿瘤物理学的基础； 3）开发基于肥大的运输线索 基于运输表型的成功个性化免疫治疗策略。我们的总体 策略完成了许多创新，包括运输作为免疫疗法的抵抗， 纳米治疗疫苗，仿生构建体，精确免疫治疗药，生物分布理论和 运输，生物分布和肿瘤生长的肿瘤物理学模型。研究项目专注于乳房 和胰腺癌，因为那些是癌症类型，面临重大临床挑战。特别是，我们会 确定纳米-DC疫苗和免疫细胞的运输，以及如何调节它们 免疫原性和治疗效率，主要关注乳腺癌（项目1）。我们也会 确定胰腺癌肿瘤微环境中的生物物理传输屏障 调节以影响免疫疗法的效率（项目2）。这两个项目都专注于免疫核管 跨越许多运输限制障碍（例如淋巴管，基质和血管泄漏）的运输。他们 还共享一组动物模型，治疗和调整剂，并且还得到了这些动物模型的支持 运输Oncophysics Core（TOC）。 CITO在拟议的资金期间的总体目标是： 1）确定乳腺和胰腺肿瘤中免疫治疗剂的转运特性； 2）到 建立用于癌症免疫治疗药的预测计算运输肿瘤物理框架； 3） 确定由热运输限制及其的治疗性抗性程度 癌症进展过程中的进化； 4）优化和个性化系统性免疫治疗性 基于前三个目标的结果策略。