Quantitative Systems Pharmacology Model Predicts Enhanced Antitumor Efficacy of Combined Cytotoxic T‑Lymphocyte-Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) Blockade in a Syngeneic Mouse Model of Breast Cancer. (PubMed, ACS Pharmacol Transl Sci) - Oct 15, 2026 - "The calibrated model captures all four treatment arms across the measured time course and supports a mechanistic explanation for the observed tumor-growth inhibition based on two distinct mechanisms: α-PD-1 lifts the PD-1/PD-L1 brake on tumor-infiltrating effector T cells, while α-CTLA-4 depletes regulatory T cells, in the tumor and in the periphery, through Fc-dependent antibody-dependent cellular cytotoxicity, a mode of action specific to the syngeneic mouse setting and distinct from the clinical mechanism of ipilimumab...A virtual cohort of 500 mice reproduces this effect, expands the fraction of strong responders under combination therapy, and identifies the balance between IL-2-driven CD4+ and CD8+ T-cell expansion, together with intrinsic tumor growth rate, as the dominant determinants of interindividual response. Because the model shares its structural architecture with our previously published human QSP-IO platform, it provides a quantitative scaffold for..."
Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • CTLA4 • IL2 • PD-L1
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Akash Patil; Aleksander S Popel; Hanwen Wang; Natsuki Furukawa; Theinmozhi Arulraj; Yu Zhang
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