68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial

作者：Xiuling Shen, Haoyi Zhou, Xin Zhou, Zongchao Liu, Zongchao Liu, Xiangxi Meng, Linyu Zhang, Yufei Song, Rui Guo, Fei Wang, Wenqing Li, Wenqing Li, Zhi Yang, Nan Li, Zhaofei Liu, Nan Li · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-53197-2 · 被引用次数：34 · 研究领域：Cancer Immunotherapy and Biomarkers、Medical Imaging Techniques and Applications、Immunotherapy and Immune Responses

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, pat...