ArticleScientific reports2026
Combined PD-1 and TIGIT blockade via siRNA enhances anti-leukemic T-cell function and promotes AML cell apoptosis.
Article in Scientific reports, 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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Abstract
This study introduces a novel siRNA-based dual checkpoint blockade approach using readily available leukoreduction filter-derived T-cells, exploring dual PD-1/TIGIT siRNA-mediated knockdown to enhance anti-leukemic activity against Acute myeloid leukemia (AML) cell lines with distinct molecular characteristics (KG-1, representing minimally differentiated AML-M0; THP-1, representing monocytic AML-M5). T-cells were isolated from leukoreduction filters (98.1% purity), activated with CD3/CD28 Dynabeads and IL-2 to upregulate PD-1 (40.5%) and TIGIT (46.4%), and transfected with siRNA (70.8% efficiency), reducing PD-1 to 11.9% and TIGIT to 19.4%. Transfected T-cells were co-cultured with AML cells at E: T ratios of 1:1, 2:1, and 5:1. Viability, cytotoxicity, IFN-γ and caspase-3 levels, and Bax/Bcl-2 mRNA expression were assessed. Dual knockdown reduced THP-1 viability to 30% and KG-1 to 40% at 5:1, with cytotoxicity increasing to 44.3% (THP-1) and 48.8% (KG-1) (P < 0.01), outperforming single knockdowns (P < 0.01). IFN-γ peaked at 80 pg/mL (THP-1, 5:1, P < 0.0001), caspase-3 rose by 70% (P < 0.0001), Bax increased 3.0-fold, and Bcl-2 decreased 70% (P < 0.001). CD8
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