CELLULAR CANCER VACCINES

细胞癌疫苗

• 批准号: 6787689
• 负责人: Mark L Tykocinski
• 金额: $ 35.27万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6787689
• 关键词: cell line; cellular immunity; clinical research; cytotoxic T lymphocyte; human subject; laboratory mouse; leukocyte activation /transformation; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; palmitates; protein transport; recombinant proteins; vaccine development

DESCRIPTION (provided by applicant): The objectives of this grant are to better understand the basic immunobiology of costimulation and to design unique cancer immunotherapeutic strategies that invoke costimulation in new ways. The strategies advocated in this application are outgrowths of a decade-long effort by our investigative team to innovate protein transfer methods that can be used for costimulator "painting," as an empowering means for achieving quantitative and combinatorial costimulator neo-expression. Thus, protein transfer represents the driving concept and distinguishing feature of this line of investigation from its inception, and it is what sets it apart from the more widespread gene therapy-based strategies that are being applied elsewhere to cancer immunotherapy. Over the course of the current grant, both the protein transfer tools and the proteins transferred have evolved, and significantly, two protein transfer modalities emerged midway through the last funding period: 1) a simple two-component protein transfer method that uses palmitated-protein A:costimulator Fcgamma1 conjugates as "costimulator paints," and enables intratumoral, multi-costimulator vaccination; and 2) a new class of soluble "trans signal converter proteins (TSCP)," which in essence constitute "injectable paints." This renewal application offers two specific aims that leverage the first of these two new protein transfer modalities: 1) Analyzing immunobiological aspects of trans intercellular costimulation, with a focus on quantitative and synergistic effects of costimulation on T cell activation thresholds, and building upon this mode of costimulation for active cancer immunotherapy -- cellular cancer vaccination, via the intratumoral, combinatorial palmitated protein A:costimulator.Fcgamma1 protein transfer method that we innovated; and 2) Exploring immunobiological aspects of the cis auto-costimulation phenomenon that we discovered, with a focus on functional and molecular features of the activation state of costimulator-painted T cells, and building upon this mode of costimulation for passive cancer immunotherapy -- conferring anti-tumor immunity via the use of adoptively-transferred, costimulator-painted T cells.

描述（由申请人提供）：这笔赠款的目标是更好地了解共刺激的基本免疫生物学，并设计以新方式调用共刺激的独特癌症免疫治疗策略。本应用程序中提倡的策略是我们的调查团队长达十年努力来创新蛋白质转移方法的生长，这些方法可用于Costimulator“绘画”，这是实现定量和组合型costimulator neo-Neo-Exptression的授权手段。因此，蛋白质转移代表了这种研究系的驾驶概念和区分特征，这是使其与更广泛的基于基因治疗的策略区分开来的，这些策略被其他地方用于癌症免疫疗法。在当前赠款的过程中，蛋白质转移工具和转移的蛋白质都已经发展起来，并且在最后一个融资期间出现了两种蛋白质转移方式：1）一种简单的两组分蛋白转移方法，它使用了棕榈树蛋白A：costimimimulator fcgamma1 Conjugations“ Costimimimimimimimimimimimimimimulator Paints and vectrim interains intermobles”和Enboss intermobles inspost inspost，又是互动的，” 2）一类新的可溶性“反式信号转换器蛋白（TSCP）”，本质上构成了“可注射涂料”。 This renewal application offers two specific aims that leverage the first of these two new protein transfer modalities: 1) Analyzing immunobiological aspects of trans intercellular costimulation, with a focus on quantitative and synergistic effects of costimulation on T cell activation thresholds, and building upon this mode of costimulation for active cancer immunotherapy -- cellular cancer vaccination, via the intratumoral, combinatorial palmitated protein答：我们创新的costimulator.fcgamma1蛋白转移方法； and 2) Exploring immunobiological aspects of the cis auto-costimulation phenomenon that we discovered, with a focus on functional and molecular features of the activation state of costimulator-painted T cells, and building upon this mode of costimulation for passive cancer immunotherapy -- conferring anti-tumor immunity via the use of adoptively-transferred, costimulator-painted T cells.