Whole-body CDS+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial
Nature medicine(2022)
摘要
Immune checkpoint inhibitors (ICIs), by reinvigorating CD8(+) T cell mediated immunity, have revolutionized cancer therapy. Yet, the systemic CD8(+) T cell distribution, a potential biomarker of ICI response, remains poorly characterized. We assessed safety, imaging dose and timing, pharmacokinetics and immunogenicity of zirconium-89-labeled, CD8-specific, one-armed antibody positron emission tomography tracer (89)ZED88082A in patients with solid tumors before and similar to 30 days after starting ICI therapy (NCT04029181). No tracer-related side effects occurred. Positron emission tomography imaging with 10 mg antibody revealed (89)ZED88082A uptake in normal lymphoid tissues, and tumor lesions across the body varying within and between patients two days after tracer injection (n = 38, median patient maximum standard uptake value (SUVmax) 5.2, IQI 4.0-7.4). Higher SUVmax was associated with mismatch repair deficiency and longer overall survival. Uptake was higher in lesions with stromal/inflamed than desert immunophenotype. Tissue radioactivity was localized to areas with immunohistochemically confirmed CD8 expression. Re-imaging patients on treatment showed no change in average (geometric mean) tumor tracer uptake compared to baseline, but individual lesions showed diverse changes independent of tumor response. The imaging data suggest enormous heterogeneity in CD8(+) T cell distribution and pharmacodynamics within and between patients. In conclusion, (89)ZED88082A can characterize the complex dynamics of CD8(+) T cells in the context of ICIs, and may inform immunotherapeutic treatments.
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关键词
Cancer imaging,Cancer immunotherapy,Tumour immunology,Biomedicine,general,Cancer Research,Metabolic Diseases,Infectious Diseases,Molecular Medicine,Neurosciences
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