ArticleJournal of translational medicine2026
Transcriptional and functional profiling reveals unique activation of Adapter CAR T cells in acute myeloid leukemia.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
backgroundChimeric antigen receptor (CAR) T cell therapy has shown great promise in treating malignant diseases, yet its efficacy is often limited by challenges such as controllability and the lack of tumor-specific antigens. Adapter CAR (AdCAR) T cells address these limitations by redirecting T cell activity through adapter molecules rather than direct interaction with tumor-associated antigens, offering an on-/off- switch mechanism and the potential for multitargeting. While functionality of AdCAR T cells has been demonstrated in various models, the underlying AdCAR T cell response to differing adapter concentration and its comparison to conventional CAR T cells remain poorly characterized.
methodsIn this study, we systematically examined adapter-dependent AdCAR T cell responses using functional assays and single-cell RNA sequencing in an acute myeloid leukemia model.
resultsAdapter concentration was found to determine AdCAR T cell activation dynamics, transcriptional states and metabolic reprogramming. At low adapter concentrations, an interferon-responsive state was observed, while high concentrations induced strong cytolytic activity, cytokine secretion, and metabolic shifts toward glycolysis and oxidative phosphorylation. Importantly, increasing adapter concentrations enhanced tumor control of sub-optimally activated AdCAR T cells, demonstrating the platform's tunability. A hallmark gene signature was identified across different adapters and target cells, comprising the interferon-responsive gene MX1 and activation-associated genes including ENO1, HSP90AB1, and RRM2.
conclusionsOur findings provide a mechanistic framework for tuning AdCAR T cell responses and offer critical insights for optimizing adapter dosing to enhance the safety and efficacy of tunable CAR T cell therapies.
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