SBIR PHASE II - TOPIC 396 - IMAGING FOR CANCER IMMUNOTHERAPIES

免疫疗法已经改变了癌症治疗，但对某些肿瘤类型的治疗反应仍然很低。尽管肿瘤内的免疫活动具有至关重要的意义，但目前还没有非侵入性的免疫监测方法来评估免疫环境和评估治疗反应。为了满足这一迫切需求，Cellsight Technologies正在开发一种针对活化T细胞的PET试剂[18F]F-AraG，作为免疫治疗反应的成像生物标志物。在I期研究中，我们在临床前模型中证明了[18F]F-AraG能够提供对单免疫和联合免疫治疗的早期反应评估。在II期，我们将重点放在临床图像分析和定量的优化和标准化上，作为[18F]F-AraG作为免疫治疗反应生物标志物的适用性的关键组成部分。在这个项目中，我们将确定肺癌患者的治疗无关变异性，以准确定义一个阈值，表明治疗诱导的信号变化。该阈值将用于对肺癌患者进行联合免疫治疗的[18F]F-AraG扫描的自动定量分析和应答图的创建。计划中的研究结果将解决定量图像分析中一些最关键的问题，并有力地推进[18F]F-AraG作为免疫治疗应答的成像生物标志物的发展。

Immunotherapy has transformed cancer treatment, but therapy response remains low for certain tumor types. Despite the vital significance of immune activity within tumors, there are currently no non-invasive immunomonitoring methods for assessment of immune contexture and assessment of response to therapy. To address this urgent need, Cellsight Technologies is developing a PET agent specific for activated T cells, [18F]F-AraG, as an imaging biomarker of immunotherapy response. In Phase I we demonstrated in preclinical models the ability of [18F]F-AraG to provide an early assessment of response to both mono and combinatorial immunotherapy. In Phase II we focus on optimization and standardization of clinical image analysis and quantitation as the crucial components of [18F]F-AraG’s suitability to serve as a biomarker of immunotherapy response. In this project, we will determine treatment-independent variability in lung cancer patients to accurately define a threshold that indicates therapy-induced signal changes. This threshold will be used for automated quantitative analysis of [18F]F-AraG scans and creation of response maps in lung cancer patients undergoing combinatorial immunotherapy. The results of the planned investigations will address some of the most critical issues in quantitative image analysis and strongly advance development of [18F]F-AraG as an imaging biomarker for response to immunotherapies.