Ga-grazytracer PET 用于评估实体瘤和淋巴瘤免疫治疗反应的非侵入性研究:一项 1/2 期临床试验。

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

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, 100142, Beijing, China.

Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Peking University Cancer Hospital & Institute, 100142, Beijing, China.

出版信息

Nat Commun. 2024 Oct 10;15(1):8791. doi: 10.1038/s41467-024-53197-2.

Abstract

To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with Ga-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 Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of Ga-grazytracer, while secondary endpoint was the relationship between Ga-grazytracer uptake and tumor immune phenotype. Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. Ga-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 Ga-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 Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

摘要

为了解决通过非侵入性方法评估患者免疫疗法疗效的临床挑战,我们使用了 Ga-grazytracer 正电子发射断层扫描(PET),该示踪剂靶向颗粒酶 B,这是一种由激活的 CD8 T 细胞分泌的关键效应分子。在这项涉及 24 名接受免疫治疗(包括免疫检查点抑制剂(单独或联合化疗)和嵌合抗原受体-T 细胞治疗)的实体瘤和淋巴瘤患者的多样化队列的 1/2 期临床试验(NCT05000372)中,我们研究了 Ga-grazytracer 的体内行为。主要终点是安全性、生物分布、颗粒酶 B 特异性以及 Ga-grazytracer 的预测实用性,次要终点是 Ga-grazytracer 摄取与肿瘤免疫表型之间的关系。Ga-grazytracer 在患者中表现出安全的特性,并特异性地靶向颗粒酶 B。Ga-grazytracer PET 对短期预后和无进展生存期的预测价值优于 RECIST 1.1 和 PERCIST 等常规评估标准。此外,在具有“非荒漠”免疫表型的肿瘤中,Ga-grazytracer 的摄取明显高于具有免疫“荒漠”表型的肿瘤,从而满足了该试验的主要和次要终点。总的来说,我们成功地使用 Ga-grazytracer PET 可视化了人类 CD8 T 细胞效应功能,为增强免疫疗法评估、患者分层和治疗计划提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c16/11467221/e3fef28dace8/41467_2024_53197_Fig1_HTML.jpg

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