Project 3

项目3

• 批准号: 6749363
• 负责人: Sandra O. Gollnick
• 金额: $ 14.82万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6749363
• 关键词: antigen presenting cell; apoptosis; basal cell carcinoma; cell line; clinical research; cytotoxic T lymphocyte; host neoplasm interaction; human subject; immunomodulators; immunopharmacology; immunoregulation; immunosuppression; inflammation; laboratory mouse; leukocyte activation /transformation; microarray technology; necrosis; neoplasm /cancer immunology; neoplasm /cancer photoradiation therapy; neoplastic growth; tumor antigens

Preclinical and clinical studies have shown that Photodynamic Therapy (PDT) augments the host immune response. We have made that novel discovery that the direct effects of Photofrin-PDT on tumor cells are sufficient to stimulate the host immune system. The overall goal of this project is understand how PDT enhances the immunogenicity of tumor cells, in vivo and in vitro. We hypothesize the PDT treatment of tumor cells, in vivo or in vitro enhances their ability to be recognized by the host immune system. We have shown that increased tumor immunogenicity can be correlated with an ability to mature and activate antigen-presenting cells and we hypothesize that Photofrin-PDT stimulates the expression of immune mediators that are able to increase the activity of antigen-presenting cells. In Specific Aim I of this proposal we will identify the factor(s) present in Photofrin-PDT generated tumor cell lysates that activate dendritic cells. We further hypothesize that the secretion of immune enhancing factors is dependent upon the initial immunogenicity of the tumor and the type of PDT regimen employed. This hypothesis will be tested in Specific Aim II. In Specific Aim III we will test whether clinical PDT, like preclinical PDT, augments the anti-tumor immune response. The studies outlined in this project will further our knowledge of how PDT affects the host immune response. An understanding of these mechanisms will potentially allow for the development of an optimal "immune enhancing" PDT protocol, which may provide a means of improving the patients ability to combat tumor and/or metastases outside the treatment field.

临床前和临床研究表明，光动力疗法（PDT）增强了宿主免疫反应。 我们已经提出了这种新发现的发现，即光蛋白-PDT对肿瘤细胞的直接影响足以刺激宿主免疫系统。该项目的总体目标是了解PDT如何增强体内和体外肿瘤细胞的免疫原性。我们假设在体内或体外对PDT治疗的PDT治疗增强了其被宿主免疫系统识别的能力。我们已经表明，增加的肿瘤免疫原性可以与成熟和激活抗原呈递细胞的能力相关，并且我们假设光蛋白-PDT刺激能够增加抗原促成细胞活性的免疫介质的表达。在该提案的特定目的I中，我们将确定光蛋白-PDT中存在的因子产生的肿瘤细胞裂解物，从而激活树突状细胞。我们进一步假设，免疫增强因素的分泌取决于 肿瘤的初始免疫原性和采用的PDT方案的类型。该假设将在特定目标II中进行检验。在特定的目标III中，我们将测试临床PDT（例如临床前PDT）是否会增强抗肿瘤免疫反应。该项目中概述的研究将进一步了解PDT如何影响宿主免疫反应。对这些机制的理解将有可能允许开发最佳的“免疫增强” PDT方案，这可能提供了提高患者对抗肿瘤和/或的能力的一种方法。 治疗领域外的转移。