IMAGING FOR EVALUATION OF CLINICAL VACCINE EFFICACY

用于评估临床疫苗功效的成像

• 批准号: 6563974
• 负责人: DAVID A. MANKOFF
• 金额: $ 29.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-19 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563974
• 关键词: active immunization; breast neoplasms; deoxyglucose; disease /disorder model; laboratory mouse; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer remission /regression; neoplasm /cancer vaccine; neoplastic growth; nonhuman therapy evaluation; thymidine; tumor antigens

Description: (provided by applicant) Phase I trials of cancer vaccines are typically performed in patients with measurable, often advanced disease. Vaccine efficacy is judged by monitoring changes in tumor size after the initiation of vaccine therapy. Using this study population, advanced stage cancer patients, few cancer vaccine trials have shown clinical efficacy. Since change in size of the tumor is a relatively late consequence of disease response or progression, and vaccine therapy may have a different effect on tumor growth or biology than chemotherapy, i.e. more cytostatic than cytotoxic, monitoring size is a crude way of assessing response. Radiotracer methods such as positron emission tomography (PET) can measure the physiologic and biochemical changes associated with an anti-tumor response, such as the local change in cellular proliferation or glucose metabolism. Although these approaches have been validated in patients receiving cytotoxic chemotherapy, their application to vaccine therapy involves potentially confounding effects, such as the possibility of increased metabolism associated with the immune response. In this pilot project we propose studies in an animal model for vaccine therapy to test and validate these promising methods of vaccine response evaluation. Perhaps, novel methods of imaging will allow some early assessment of vaccine clinical efficacy prior to the institution of large-scale trials. Our hypothesis is that the quantitative changes in cellular proliferation measured by labeled thymidine will accurately reflect tumor response early in the course vaccine therapy, even if that response is cytostatic. A decline in FDG uptake over the course of treatment may also indicate a tumor response; however, there may an early increase in metabolism associated with immune response at the tumor site. The specific aims of this pilot project are to: (1) Determine whether changes in FDG and thymidine uptake correlate with tumor growth or regression in a murine breast cancer model responsive to antigen specific immunization. (2) Determine whether changes in FDG and thymidine uptake predict tumor shrinkage or growth at an earlier time point than standard measures of tumor size. (3) Determine if an increase in FDG uptake tumor occurs with the initiation of an immune response at the tumor site. We anticipate that the studies described here will lead to a pilot Phase I trial of techniques in patients with measurable tumors undergoing HER2 vaccination.

说明：（申请人提供） 癌症疫苗的I期试验通常在以下患者中进行： 可测量的，通常是晚期的疾病。通过监测判断疫苗效力 疫苗治疗开始后肿瘤大小的变化。使用此 研究人群，晚期癌症患者，很少有癌症疫苗试验 已显示出临床疗效。由于肿瘤大小的变化是一个 疾病反应或进展相对较晚的后果，以及疫苗 治疗对肿瘤生长或生物学的影响可能不同于 化疗，即比细胞毒性更多的细胞抑制，监测大小是一个粗略的 评估反应的方式。放射性示踪方法，如正电子发射 断层扫描（PET）可以测量生理和生化变化 与抗肿瘤反应相关，例如细胞内的局部变化， 增殖或葡萄糖代谢。虽然这些方法已经 在接受细胞毒性化疗的患者中得到验证， 疫苗治疗涉及潜在的混杂效应，例如 与免疫反应相关的代谢增加的可能性。在 在这个试点项目中，我们提出了一个疫苗治疗的动物模型研究， 来测试和验证这些有前途的疫苗反应评估方法。 也许，新的成像方法将允许对疫苗进行一些早期评估。 在进行大规模试验之前的临床疗效。 我们的假设是细胞增殖的数量变化 通过标记的胸苷测量将准确地反映早期的肿瘤反应， 疫苗治疗过程中，即使反应是细胞抑制性的。下降 在治疗过程中FDG摄取也可以指示肿瘤反应; 然而，可能存在与免疫相关代谢的早期增加， 肿瘤部位的反应。该试点项目的具体目标是： (1)确定FDG和胸苷摄取的变化是否与肿瘤相关 在对抗原有反应的鼠乳腺癌模型中的生长或消退 特殊免疫。 (2)确定FDG和胸苷摄取的变化是否预测肿瘤 在比肿瘤的标准测量更早的时间点收缩或生长 尺寸 (3)确定FDG摄取肿瘤是否随着开始 肿瘤部位的免疫反应 我们预计，这里所描述的研究将导致一个试点阶段I 在接受HER 2治疗的可测量肿瘤患者中进行的技术试验 预防针