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

Author

Listed:
  • Xiuling Shen

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Haoyi Zhou

    (Peking University Health Science Center)

  • Xin Zhou

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Zongchao Liu

    (Peking University Cancer Hospital & Institute)

  • Xiangxi Meng

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Linyu Zhang

    (Peking University Health Science Center)

  • Yufei Song

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Rui Guo

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Fei Wang

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Kui Li

    (Peking University Health Science Center)

  • Wenqing Li

    (Peking University Cancer Hospital & Institute)

  • Zhi Yang

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

  • Zhaofei Liu

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute
    Peking University Health Science Center
    Peking University Third Hospital)

  • Nan Li

    (Peking University Cancer Hospital & Institute
    Peking University Cancer Hospital & Institute)

Abstract

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, patient stratification and treatment planning.

Suggested Citation

  • Xiuling Shen & Haoyi Zhou & Xin Zhou & Zongchao Liu & Xiangxi Meng & Linyu Zhang & Yufei Song & Rui Guo & Fei Wang & Kui Li & Wenqing Li & Zhi Yang & Zhaofei Liu & Nan Li, 2024. "68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53197-2
    DOI: 10.1038/s41467-024-53197-2
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