{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:17:05Z","timestamp":1788239825852,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sialylated immunoglobulin G (SIA-IgG) has emerged as a novel therapeutic target selectively overexpressed in epithelial-derived malignancies. The humanized monoclonal antibody SIG001 binds specifically to tumor-associated SIA-IgG and is regarded as a promising first-in-class candidate for the broad-spectrum treatment of epithelial cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The pharmacokinetic (PK) behavior of SIG001 was evaluated in both cynomolgus monkeys and mice following intravenous administration. Utilizing modeling approaches, we projected the first-in-human (FIH) starting dose and the human pharmacologically active dose (PAD) from preclinical datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In cynomolgus monkeys, single-dose PK was assessed at 5, 15, and 30\u00a0mg\/kg, while in mice, doses of 5, 10, and 20\u00a0mg\/kg were investigated. Data from both species were well characterized by a two-compartment model with linear elimination kinetics; human PK parameters were extrapolated from the monkey studies.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies demonstrated that SIG001, at concentrations up to 50\u00a0\u03bcg\/mL, did not elicit significant cytokine release from human peripheral blood mononuclear cells (PBMCs), establishing this concentration as a safety threshold for FIH dose estimation. Based on simulations incorporating moderate PK variability, a maximum recommended starting dose of 0.15\u00a0mg\/kg, administered biweekly, was identified. Efficacy studies in murine xenograft models revealed a plateaued, dose-dependent antitumor response across the range of 2.5\u201310\u00a0mg\/kg, indicative of maximal receptor occupancy and a saturated therapeutic effect. The translational scaling of murine PK profiles yielded human equivalent doses (HEDs), with predicted PAD values ranging from 1.8 to 7.0\u00a0mg\/kg.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The preclinical investigations delineate the PK profile and antitumor activity of SIG001. The quantitative translation of animal data into human PK and exposure\u2013response expectations provides a rational foundation for clinical development and supports informed decision-making in the design of early-phase trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1904283","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:27:34Z","timestamp":1788236854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical pharmacokinetic modeling and clinical translation of SIG001, a novel anti-cancer therapeutic antibody targeting on cancer-derived sialylated IgG"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingyu","family":"Yao","sequence":"first","affiliation":[{"name":"Clinical Trial Center, Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Beijing Key Laboratory of Clinical Pharmacology and Translation of Innovative Drugs, Peking University First Hospital","place":["Beijing, China"]},{"name":"Department of Pharmacy, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10928-008-9094-4","article-title":"Likelihood based approaches to handling data below the quantification limit using NONMEM VI","volume":"35","author":"Ahn","year":"2008","journal-title":"J. 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