{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:52:01Z","timestamp":1791553921986,"version":"4.3.4"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA138264"],"award-info":[{"award-number":["R01CA138264"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA196701"],"award-info":[{"award-number":["R01CA196701"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005979","name":"Lustgarten Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100005979","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune-checkpoint inhibitors targeting PD-1 and CTLA-4 have transformed cancer therapy, yet most patients still fail to respond, and the reasons remain incompletely understood. To dissect this heterogeneity and support translational development, we built a preclinical quantitative systems pharmacology model of \u03b1-PD-1, \u03b1-CTLA-4, and their combination in syngeneic mouse models, calibrating it jointly against vehicle, monotherapy, and combination tumor growth data. 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: \u03b1-PD-1 lifts the PD-1\/PD-L1 brake on tumor-infiltrating effector T cells, while \u03b1-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. Because the two pathways engage different cell populations, the combination produces antitumor activity beyond what either drug achieves alone, with synergy analysis indicating approximately 4-fold reciprocal potency synergy. 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 guiding preclinical-to-clinical evaluation of checkpoint-combination strategies.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00347","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:01:27Z","timestamp":1789034487000},"page":"2877-2888","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Systems\nPharmacology Model Predicts Enhanced\nAntitumor Efficacy of Combined Cytotoxic T-Lymphocyte-Associated\nProtein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) Blockade\nin a Syngeneic Mouse Model of Breast Cancer"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3643-6589","authenticated-orcid":true,"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5480-431X","authenticated-orcid":true,"given":"Hanwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5771-917X","authenticated-orcid":true,"given":"Natsuki","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Patil","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-7512","authenticated-orcid":true,"given":"Theinmozhi","family":"Arulraj","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander S.","family":"Popel","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]},{"name":"Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21205"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"issue":"4","key":"2026100909105159000_cit1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade\nof immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"issue":"8","key":"2026100909105159000_cit2","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1016\/j.cell.2023.03.006","article-title":"Immune checkpoint\ntherapy\u2013current perspectives and future directions","volume":"186","author":"Sharma","year":"2023","journal-title":"Cell"},{"key":"2026100909105159000_cit3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3389\/fonc.2018.00086","article-title":"Anti-PD-1 and Anti-CTLA-4 Therapies\nin Cancer: Mechanisms of Action, Efficacy, and Limitations","volume":"8","author":"Seidel","year":"2018","journal-title":"Front. Oncol."},{"issue":"2","key":"2026100909105159000_cit4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1208\/s12248-021-00574-0","article-title":"Cancer Immunotherapy\nUpdate: FDA-Approved Checkpoint Inhibitors and\nCompanion Diagnostics","volume":"23","author":"Twomey","year":"2021","journal-title":"AAPS J."},{"issue":"10265","key":"2026100909105159000_cit5","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1016\/S0140-6736(20)32531-9","article-title":"KEYNOTE-355\nInvestigators. Pembrolizumab plus chemotherapy versus placebo plus\nchemotherapy for previously untreated locally recurrent inoperable\nor metastatic triple-negative breast cancer (KEYNOTE-355): a randomised,\nplacebo-controlled, double-blind, phase 3 clinical trial","volume":"396","author":"Cortes","year":"2020","journal-title":"Lancet"},{"issue":"1","key":"2026100909105159000_cit6","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab\nor Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl.\nJ. Med."},{"issue":"3","key":"2026100909105159000_cit7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions\nof the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat. Rev. Immunol."},{"issue":"1","key":"2026100909105159000_cit8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4:\na moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"issue":"4","key":"2026100909105159000_cit9","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S1074-7613(00)80366-0","article-title":"The emerging role\nof CTLA-4 as an immune attenuator","volume":"7","author":"Thompson","year":"1997","journal-title":"Immunity"},{"issue":"5","key":"2026100909105159000_cit10","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/1074-7613(94)90071-X","article-title":"CTLA-4\ncan function as a negative regulator of T cell activation","volume":"1","author":"Walunas","year":"1994","journal-title":"Immunity"},{"issue":"9","key":"2026100909105159000_cit11","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1084\/jem.20130579","article-title":"Fc-dependent depletion\nof tumor-infiltrating\nregulatory T cells co-defines the efficacy of anti-CTLA-4 therapy\nagainst melanoma","volume":"210","author":"Simpson","year":"2013","journal-title":"J. Exp. Med."},{"issue":"8","key":"2026100909105159000_cit12","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/nrd4591","article-title":"Combination\ncancer immunotherapy\nand new immunomodulatory targets","volume":"14","author":"Mahoney","year":"2015","journal-title":"Nat. Rev.\nDrug Discovery"},{"issue":"21","key":"2026100909105159000_cit13","doi-asserted-by":"publisher","first-page":"9543","DOI":"10.1128\/MCB.25.21.9543-9553.2005","article-title":"CTLA-4 and PD-1 receptors inhibit T-cell activation\nby distinct mechanisms","volume":"25","author":"Parry","year":"2005","journal-title":"Mol. Cell. Biol."},{"issue":"45","key":"2026100909105159000_cit14","doi-asserted-by":"publisher","first-page":"22699","DOI":"10.1073\/pnas.1821218116","article-title":"Combination anti-CTLA-4 plus anti-PD-1\ncheckpoint blockade utilizes cellular mechanisms partially distinct\nfrom monotherapies","volume":"116","author":"Wei","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.\nS. A."},{"issue":"8","key":"2026100909105159000_cit15","doi-asserted-by":"publisher","first-page":"104702","DOI":"10.1016\/j.isci.2022.104702","article-title":"Dynamics\nof tumor-associated macrophages in a quantitative systems pharmacology\nmodel of immunotherapy in triple-negative breast cancer","volume":"25","author":"Wang","year":"2022","journal-title":"iScience"},{"issue":"5","key":"2026100909105159000_cit16","doi-asserted-by":"publisher","first-page":"190366","DOI":"10.1098\/rsos.190366","article-title":"In silico simulation of a clinical\ntrial with anti-CTLA-4\nand anti-PD-L1 immunotherapies in metastatic breast cancer using a\nsystems pharmacology model","volume":"6","author":"Wang","year":"2019","journal-title":"R. Soc. Open Sci."},{"issue":"1","key":"2026100909105159000_cit17","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1021\/acsptsci.0c00178","article-title":"Quantitative Systems Pharmacology Modeling of PBMC-Humanized\nMouse to Facilitate Preclinical Immuno-oncology Drug Development","volume":"4","author":"Ma","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"issue":"7","key":"2026100909105159000_cit18","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/psp4.12800","article-title":"Quantitative systems\npharmacology modeling provides insight into inter-mouse variability\nof Anti-CTLA4 response","volume":"11","author":"Qiao","year":"2022","journal-title":"CPT:Pharmacometrics\nSyst. Pharmacol."},{"issue":"5","key":"2026100909105159000_cit19","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s10928-023-09884-6","article-title":"Towards a platform\nquantitative systems pharmacology (QSP) model for preclinical to clinical\ntranslation of antibody drug conjugates (ADCs)","volume":"51","author":"Scheuher","year":"2024","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"issue":"1","key":"2026100909105159000_cit20","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11095-019-2745-x","article-title":"Intraperitoneal\nRoute of Drug Administration: Should it Be Used in Experimental Animal\nStudies?","volume":"37","author":"Al Shoyaib","year":"2020","journal-title":"Pharm. Res."},{"key":"2026100909105159000_cit21","doi-asserted-by":"publisher","first-page":"101405","DOI":"10.1016\/j.tranon.2022.101405","article-title":"Anti-CTLA-4\nand anti-PD-1 immunotherapies\nrepress tumor progression in preclinical breast and colon model with\nindependent regulatory T cells response","volume":"20","author":"Rupp","year":"2022","journal-title":"Transl.\nOncol."},{"issue":"2","key":"2026100909105159000_cit22","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/eji.1830180221","article-title":"The half-lives of serum\nimmunoglobulins in adult mice","volume":"18","author":"Vieira","year":"1988","journal-title":"Eur. J. Immunol."},{"issue":"1","key":"2026100909105159000_cit23","doi-asserted-by":"publisher","first-page":"4607","DOI":"10.1038\/s41467-021-24789-z","article-title":"MuSyC is\na consensus framework that unifies multi-drug synergy metrics for\ncombinatorial drug discovery","volume":"12","author":"Wooten","year":"2021","journal-title":"Nat. Commun."},{"issue":"9","key":"2026100909105159000_cit24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161779","article-title":"Preclinical Development\nof Ipilimumab\nand Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro\nFunctional Studies, and Cynomolgus Macaque Toxicology","volume":"11","author":"Selby","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"2026100909105159000_cit25","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1158\/2326-6066.CIR-13-0013","article-title":"Anti-CTLA-4 Antibodies\nof IgG2a Isotype\nEnhance Antitumor Activity through Reduction of Intratumoral Regulatory\nT Cells","volume":"1","author":"Selby","year":"2013","journal-title":"Cancer Immunol. Res."},{"issue":"16_Supplement","key":"2026100909105159000_cit26","doi-asserted-by":"publisher","first-page":"4552","DOI":"10.1158\/1538-7445.AM2020-4552","article-title":"Abstract 4552: Preclinical characterization\nof BMS-986218, a novel\nnonfucosylated anti\u2013CTLA-4 antibody designed to enhance antitumor\nactivity","volume":"80","author":"Engelhardt","year":"2020","journal-title":"Cancer Res."},{"issue":"4","key":"2026100909105159000_cit27","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1158\/1078-0432.CCR-18-0762","article-title":"Anti-CTLA-4\nImmunotherapy Does Not Deplete FOXP3(+) Regulatory T Cells (Tregs)\nin Human Cancers","volume":"25","author":"Sharma","year":"2019","journal-title":"Clin. Cancer Res."},{"issue":"19","key":"2026100909105159000_cit28","doi-asserted-by":"publisher","first-page":"6140","DOI":"10.1073\/pnas.1417320112","article-title":"Ipilimumab-dependent\ncell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical\nmonocytes in melanoma patients","volume":"112","author":"Romano","year":"2015","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"issue":"6","key":"2026100909105159000_cit29","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1023\/A:1014414520282","article-title":"General pharmacokinetic model for drugs exhibiting\ntarget-mediated drug disposition","volume":"28","author":"Mager","year":"2001","journal-title":"J. Pharmacokinet.\nPharmacodyn."},{"issue":"19","key":"2026100909105159000_cit30","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1200\/JCO.2009.26.7609","article-title":"Phase I study of\nsingle-agent anti-programmed death-1 (MDX-1106) in refractory solid\ntumors: safety, clinical activity, pharmacodynamics, and immunologic\ncorrelates","volume":"28","author":"Brahmer","year":"2010","journal-title":"J. Clin. Oncol."},{"issue":"7","key":"2026100909105159000_cit31","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s40262-019-00748-2","article-title":"Clinical Pharmacokinetics and Pharmacodynamics\nof Immune\nCheckpoint Inhibitors","volume":"58","author":"Centanni","year":"2019","journal-title":"Clin. Pharmacokinet."},{"issue":"1","key":"2026100909105159000_cit32","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/s12885-019-5785-z","article-title":"The safety and tolerability\nof combined immune checkpoint\ninhibitors (anti-PD-1\/PD-L1 plus anti-CTLA-4): a systematic review\nand meta-analysis","volume":"19","author":"Gu","year":"2019","journal-title":"BMC Cancer"},{"issue":"9","key":"2026100909105159000_cit33","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s12276-020-00500-y","article-title":"Combination\nof anti-angiogenic\ntherapy and immune checkpoint blockade normalizes vascular-immune\ncrosstalk to potentiate cancer immunity","volume":"52","author":"Lee","year":"2020","journal-title":"Exp.\nMol. Med."},{"key":"2026100909105159000_cit34","doi-asserted-by":"publisher","first-page":"940567","DOI":"10.3389\/fphar.2022.940567","article-title":"Chemotherapy Combined\nWith Immunotherapy as a First-Line Treatment Brings Benefits to Patients\nWith Lung Squamous Cell Carcinoma but Different Risks of Adverse Reactions:\nA Systematic Review and Meta-Analysis","volume":"13","author":"Chen","year":"2022","journal-title":"Front.\nPharmacol."},{"issue":"2","key":"2026100909105159000_cit35","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002100","article-title":"Quantitative\nsystems pharmacology model predictions for efficacy of atezolizumab\nand nab-paclitaxel in triple-negative breast cancer","volume":"9","author":"Wang","year":"2021","journal-title":"J. Immunother. Cancer"},{"issue":"5","key":"2026100909105159000_cit36","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1021\/acsptsci.3c00008","article-title":"Combining multikinase\ntyrosine kinase\ninhibitors targeting the vascular endothelial growth factor and cluster\nof differentiation 47 signaling pathways is predicted to increase\nthe efficacy of antiangiogenic combination therapies","volume":"6","author":"Zhang","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"issue":"45","key":"2026100909105159000_cit37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2410911121","article-title":"Virtual patient analysis identifies\nstrategies to improve\nthe performance of predictive biomarkers for PD-1 blockade","volume":"121","author":"Arulraj","year":"2024","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"26","key":"2026100909105159000_cit38","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg0289","article-title":"A transcriptome-informed QSP model of metastatic triple-negative\nbreast cancer identifies predictive biomarkers for PD-1 inhibition","volume":"9","author":"Arulraj","year":"2023","journal-title":"Sci. Adv."},{"issue":"3","key":"2026100909105159000_cit39","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1158\/0008-5472.CAN-03-2524","article-title":"Predictive pharmacokinetic-pharmacodynamic modeling\nof tumor growth kinetics in xenograft models after administration\nof anticancer agents","volume":"64","author":"Simeoni","year":"2004","journal-title":"Cancer Res."},{"issue":"1","key":"2026100909105159000_cit40","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/psp4.12139","article-title":"Model-Based\nCharacterization of the Pharmacokinetics of Pembrolizumab: A Humanized\nAnti\u2013PD-1 Monoclonal Antibody in Advanced Solid Tumors","volume":"6","author":"Ahamadi","year":"2017","journal-title":"CPT:Pharmacometrics Syst. Pharmacol."},{"issue":"1","key":"2026100909105159000_cit41","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1111\/bcp.12323","article-title":"Model-Based Clinical Pharmacology Profiling of Ipilimumab in Patients\nwith Advanced Melanoma","volume":"78","author":"Feng","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"5","key":"2026100909105159000_cit42","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1080\/19420862.2018.1462429","article-title":"Linear pharmacokinetic\nparameters for monoclonal antibodies are similar within a species\nand across different pharmacological targets: A comparison between\nhuman, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling\napproach","volume":"10","author":"Betts","year":"2018","journal-title":"mAbs"},{"issue":"10","key":"2026100909105159000_cit43","doi-asserted-by":"publisher","first-page":"3850","DOI":"10.1002\/jps.21682","article-title":"Pharmacokinetic\nAllometric Scaling of Antibodies: Application to the First-In-Human\nDose Estimation","volume":"98","author":"Mahmood","year":"2009","journal-title":"J. Pharm. Sci."},{"issue":"3","key":"2026100909105159000_cit44","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/BF00199929","article-title":"The intraperitoneal\ndelivery of radiolabeled\nmonoclonal antibodies: studies on the regional delivery advantage","volume":"26","author":"Wahl","year":"1988","journal-title":"Cancer Immunol., Immunother."}],"container-title":["ACS Pharmacology &amp; Translational\nScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsptsci.6c00347","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2877\/68468452\/acsptsci.6c00347.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2877\/68468452\/acsptsci.6c00347.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:22:55Z","timestamp":1791552175000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article\/9\/10\/2877\/5427515\/Quantitative-Systems-Pharmacology-Model-Predicts"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,10]]},"published-print":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1021\/acsptsci.6c00347","relation":{},"ISSN":["2575-9108"],"issn-type":[{"value":"2575-9108","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}