Core B: Biological Models, Multiplexed Optical Biopsy, Molecular Pathology, and Biostatistics Core

摘要 生物模型，多路光学活检，分子病理学，生物统计学核心，核心B， 将新的生物模型与新开发的生化和成像分析平台集成在一起，以实现 计划项目中设想的治疗方法的开发。核心B的目标是提供 服务和研究平台，提高显微镜、生物统计学和病理学技术的效率 由所有四个计划项目使用。核心B还将协调集中传达生物统计数据和 支持实验设计和临床前和临床结果解释的病理学服务。 总的来说，Core的目标是开发新的灵活和可扩展的技术来治疗皮肤癌和胰腺癌 与方案项目建立伙伴关系，进一步推动该领域走向个性化和个性化 通过通知免疫检查点抑制的时间进行治疗。这可能会产生巨大的影响 对定制的、精确的免疫检查点抑制治疗的长期影响，使其最大化 在降低毒性的同时还能发挥功效。Core B的这一研发组件将提供新的癌症 用于推进该计划项目的模型和肿瘤成像技术。核心B是交互式的 所有计划项目和每个项目都将利用核心B资源和服务，如下所示： 新开发的患者从皮肤活检(项目1)和胰腺癌获得的体外器官模型 废弃的手术组织(项目3)；先前建立的具有体内免疫活性的小鼠皮肤模型 癌症(项目1)和胰腺癌(项目3)；以及新的视频多路复用活体显微内窥镜 (项目1、2和3)是在上一个供资周期内开发和验证的。此外，核心 在专家的指导下，为项目1、2和3提供生物统计和分子病理学服务 生物统计学家以及在皮肤癌和胰腺癌方面有专长的病理学家。强大的基础设施 MGH和梅奥诊所免费提供，使这一雄心勃勃的核心B计划成为可能 最低限度的P01资源。显微镜支持包括独特的硬件和软件，具有严格的 对于高光谱多路传输的验证，以及对可操作的、定制设计的系统的这种使用 不仅引入了独特的功能，而且与商业解决方案相比还节省了成本。总而言之， 核心B拥有必要的基础设施和人员，以最大限度地提高计划项目在 光动力引发免疫检查点抑制的新组合方案的发现 有潜力提供持久的治疗结果并改善皮肤和胰腺的生活质量 癌症患者。

ABSTRACT The Biological Models, Multiplexed Optical Biopsy, Molecular Pathology, and Biostatistics Core, Core B, integrates novel biological models with newly developed biochemical and imaging assay platforms to enable the development of the treatments envisioned in the Program Projects. The objective of Core B is to provide a service and research platform to increase the efficiency of microscopy, biostatistics and pathology techniques used by all four Program Projects. Core B will also coordinate centrally communicating biostatistics and pathological services to support experimental design and the interpretation of preclinical and clinical results. Collectively, the Core aims to develop new flexible and scalable technologies for skin and pancreatic cancer in partnership with the Program Projects to move the field further towards personalized and individualized therapies by informing the timing of immune checkpoint inhibition. This could have a tremendous impact with implications in the long run for customized, precision immune checkpoint inhibition treatments that maximize efficacy while reducing toxicity. This research and development component of Core B will provide novel cancer models and tumor imaging technologies for the advancement of the Program Projects. Core B is interactive with all of the Program Projects and each Project will leverage Core B resources and services, as follows: newly developed patient-derived in vitro organoid models from skin biopsies (Project 1) and pancreatic cancer discarded surgical tissue (Project 3); previously established in vivo immunocompetent mouse models of skin cancer (Project 1) and pancreatic cancer (Project 3); and, novel video multiplexed in vivo microendoscopy (Projects 1, 2, and 3) that was developed and validated during the previous funding cycle. In addition, the Core provides biostatistics and molecular pathology services to Projects 1, 2, and 3, with guidance from expert biostatisticians as well as pathologists with expertise in skin and pancreatic cancer. The strong infrastructure at MGH and the Mayo Clinic available at no costs makes this ambitious plan for Core B possible within the minimal resources of the P01. The microscopy support includes unique hardware and software, with rigorous validations, for hyperspectral multiplexing and this use of operational, custom-designed systems also introduces not only unique capabilities but also cost savings compared to commercial solutions. Collectively, Core B has the necessary infrastructure and personnel to maximize the success of the Program Projects in the discovery of novel combination regimens for photodynamic priming of immune checkpoint inhibition with potential to provide durable treatment outcomes and to improve quality of life for both skin and pancreatic cancer patients.