靶受体表达决定 eciskafusp alfa 在来自 CPI 初治患者的匹配 PBMC 与 TIL 中对 CD8⁺ T 细胞的选择性瘤内靶向

This study provides a comprehensive ex-vivo characterization of PD1-IL2v's target landscape using matched peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) from patients across seven solid tumor indications.

We confirmed that the TIL compartment is significantly enriched with both stem-like CD8 + T cells and immunosuppressive regulatory T cells (Tregs). Notably, PD-1 receptor density was increased up to three-fold on CD8 + TILs compared to PBMCs, establishing the basis for preferential intra-tumoral targeting. Ex-vivo assays demonstrated that PD1-IL2v preferentially targets CD8 + TIL subsets (stem-like and effector) over Tregs. This preferential targeting translated into superior biological activity, with PD1-IL2v inducing higher STAT5 phosphorylation (STAT5-P) in stem-like and effector CD8 + T cells compared to Tregs, confirming the intended cis -targeting and enhanced IL-2R agonism. DISCUSSION: These findings provide translational validation for PD1-IL2v's mechanism, demonstrating selective intra-tumoral immune stimulation while minimizing Treg activation. This characterization identifies PD-1 receptor density and subset prevalence as critical factors for drug activity and represents potentially useful biomarkers for predicting patient responsiveness and guiding patient selection.