IMAGING FOR EVALUATION OF CLINICAL VACCINE EFFICACY

描述：(申请人提供) 癌症疫苗的I期试验通常在患有癌症的患者中进行 可测量的，通常是严重的疾病。疫苗的效力是通过监测来判断的 疫苗治疗开始后肿瘤大小的变化。使用这个 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。因为肿瘤大小的改变是一种 疾病反应或进展的相对较晚的后果，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，即更多的细胞抑制而不是细胞毒性，监测规模是粗略的 评估回应的方式。正电子发射等放射性示踪方法 断层扫描(PET)可以测量人体的生理和生化变化。 与抗肿瘤反应有关，例如细胞的局部变化 增殖或葡萄糖代谢。尽管这些方法已经被 在接受细胞毒性化疗的患者中得到验证，它们的应用 疫苗疗法涉及潜在的混杂效应，例如 与免疫反应相关的新陈代谢增加的可能性。在……里面 在这个试点项目中，我们提议对疫苗治疗的动物模型进行研究。 测试和验证这些有前景的疫苗反应评估方法。 也许，新的成像方法将使疫苗的一些早期评估成为可能。 在建立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 用标记胸腺嘧啶核苷测定将准确地反映肿瘤早期反应 疗程疫苗疗法，即使这种反应是细胞抑制。……的下降 治疗过程中摄取FDG也可能预示着肿瘤的反应； 然而，与免疫相关的新陈代谢可能会在早期增加。 肿瘤部位的反应。这一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 抗原反应的小鼠乳腺癌模型的生长或消退 特异性免疫。 (2)确定FDG和胸腺嘧啶核苷摄取的变化是否预测肿瘤 缩小或生长的时间点早于肿瘤的标准测量标准 尺码。 (3)确定FDG摄取增加是否与肿瘤的启动有关 肿瘤部位的免疫反应。 我们预计，这里描述的研究将导致第一阶段的试点 可测量肿瘤患者接受HER2治疗的技术试验 接种疫苗。

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.