For example, increased CD8 + cell density in 25 paired tumor biopsy samples collected after 20–120 days pembrolizumab treatment was associated with response 11. Most data are available for patients with advanced melanoma with biopsy samples obtained at different time points following the start of ICIs. An ICI treatment-emergent increase in CD8 + T cell density in tumor biopsy samples has also been associated with tumor response. Their presence in the tumor is associated with responses to ICIs across several tumor types 6, 7, 8, 9, 10. However, no single biomarker or combination of biomarkers accurately predicts response to ICI.ĬD8 + T cells play an essential role in tumor cell destruction by the immune system. These include programmed death-ligand 1 (PD-L1) expression, tumor mutational burden, deficiency of mismatch repair (dMMR) proteins and a T cell-inflamed gene expression profile 4, 5, 6. Several biomarkers have been identified to select patients for ICI 3. This highlights the clinical need for tools to optimize treatment strategies for individual patients. A combination with another ICI or other medicines can improve response rates but can also increase the risk of adverse events (AEs) 1. However, response rates vary, and only a subset of patients benefits. T cell-enhancing immune checkpoint inhibitors (ICIs) have gained their place in cancer treatment with impressive, durable antitumur efficacy in a remarkable variety of tumor types 1, 2, 3. In conclusion, 89ZED88082A can characterize the complex dynamics of CD8 + T cells in the context of ICIs, and may inform immunotherapeutic treatments. The imaging data suggest enormous heterogeneity in CD8 + T cell distribution and pharmacodynamics within and between patients.
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. Tissue radioactivity was localized to areas with immunohistochemically confirmed CD8 expression. Uptake was higher in lesions with stromal/inflamed than desert immunophenotype. Higher SUV max was associated with mismatch repair deficiency and longer overall survival. Positron emission tomography imaging with 10 mg antibody revealed 89ZED88082A 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 (SUV max) 5.2, IQI 4.0–7.4). We assessed safety, imaging dose and timing, pharmacokinetics and immunogenicity of zirconium-89-labeled, CD8-specific, one-armed antibody positron emission tomography tracer 89ZED88082A in patients with solid tumors before and ~30 days after starting ICI therapy (NCT04029181). Yet, the systemic CD8 + T cell distribution, a potential biomarker of ICI response, remains poorly characterized. Immune checkpoint inhibitors (ICIs), by reinvigorating CD8 + T cell mediated immunity, have revolutionized cancer therapy. Nature Medicine volume 28, pages 2601–2610 ( 2022) Cite this article
600 SQUARE FEET VISUALIZED TRIAL
Whole-body CD8 + T cell visualization before and during cancer immunotherapy: a phase 1/2 trial
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