Transport Oncophysics Core

运输肿瘤物理学核心-摘要 癌症免疫疗法最近已被证明是相当有效的治疗肺癌 和黑色素瘤，但对于其他适应症，包括乳腺癌和胰腺癌，其应用仍有待进一步研究。 考虑到后者癌症带来的额外挑战（低免疫原性），我们认为 优化药物和免疫细胞在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。因此，运输的影响 现象（物理时空参数和肿瘤畸变）对免疫效力的影响 应该考虑开发有效的免疫疗法。拟议的中心 免疫转运肿瘤物理学（CITO）的重点是确定这些运输现象 在乳腺和胰腺肿瘤模型中，为了改善免疫疗法通过组织的转运， 并最终能够为患者合理设计最佳免疫方案， 个体化治疗支持CITO及其2个研究项目[项目1：癌症的传播 纳米树突状（DC）疫苗;肿瘤微环境中生物物理屏障的项目2]， 运输肿瘤物理学核心（TOC）将提供成像，分析，定量和独特的肿瘤物理学 基于肿瘤物理学建模的计算工具， 运输和生物分布理论（TBT）。技术性贸易壁垒将传统工具的界限 研究药代动力学和功效关系，并创建新的精确免疫工具， 为病人量身定制合理的治疗方案。TOC的总体假设是， 组织的性质（作为生物屏障）是决定生物分布的决定因素。 免疫治疗剂，特异性生物靶向识别的上游（但与之协同）。分布 影响疗效、不良反应和耐药现象，最终影响患者结局。TOC将 汇总这两个项目的数据，然后提供具体服务，以合理开发和 改善免疫治疗剂的递送。TOC将为项目提供三大服务： (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 模型潜在的逻辑是，体内和病理成像提供了细胞的快照和时间间隔。 治疗剂的生物分布。对各个时间点和运输动态的量化将产生 用于计算模型的时间序列数据，以开发时空生物分布，其是以下函数： 肿瘤微环境、免疫学形态及其在治疗中的转运特性 相关的时间尺度。免疫治疗剂的生物分布和控制转运的佐剂的作用 免疫治疗的有效性将与治疗结果和肿瘤生长相关。

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.