{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:46:44Z","timestamp":1766040404540,"version":"3.48.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"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":"\n Objective<\/jats:title>\n The aim of this study is to evaluate the similarity of affinity, pharmacokinetics, and immunogenicity shared by HS630 and trastuzumab emtansine (T-DM1).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In vitro<\/jats:italic>\n , affinity was tested using a Biacore\u2122 T200 apparatus.\n In vivo<\/jats:italic>\n studies were conducted on tumor-bearing mice and cynomolgus monkeys in the context of different dosages and frequencies of administration. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of total antibody (including naked antibody and antibody\u2013drug conjugate (ADC)) and the ADC of HS630 and Kadcyla\u00ae. Furthermore, HPLC\u2013MS\/MS was used to determine the concentration of free DM1. The bridge ELISA method was performed to determine anti-drug antibody for immunogenicity analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In vitro<\/jats:italic>\n , HS630 and Kadcyla\u00ae exhibited similar binding affinities for human epidermal growth factor receptor 2 (HER2), with K\n D<\/jats:sub>\n values of 6.372\u00a0E-11M and 9.424\u00a0E-11 M, respectively. After injecting 10\u00a0mg\u00b7kg\n \u22121<\/jats:sup>\n of HS630 and Kadcyla\u00ae into tumor-bearing mice, the concentration of total antibody and ADC in serum reached its peak concentration at 5\u00a0min, and the concentration of total antibody reached its peak concentration at 24\u00a0h in the tumor. Meanwhile, in cynomolgus monkeys, the concentration of total antibody and ADC of HS630 exhibited non-linear pharmacokinetic characteristics following a single intravenous administration of HS630 at 0.33\u00a0mg\u00b7kg\n \u22121<\/jats:sup>\n , 1\u00a0mg\u00b7kg\n \u22121<\/jats:sup>\n , and 3\u00a0mg\u00b7kg\n \u22121<\/jats:sup>\n , respectively. No significant drug accumulation was observed after continuous intravenous administration of 3\u00a0mg\u00b7kg\n \u22121<\/jats:sup>\n HS630. Biosimilarity evaluation showed that HS630 met the criteria for C\n max<\/jats:sub>\n and AUC(0-t) geometric mean ratios with Kadcyla\u00ae in the serum of tumor-bearing mice, as well as tumors and serum of cynomolgus monkey. No anti-drug antibody was detected in the serum samples obtained from cynomolgus monkeys after intravenous administration of HS630 and Kadcyla\u00ae.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n HS630 and originator drug Kadcyla\u00ae exhibit pharmacokinetic similarity in tumor-bearing mice and cynomolgus monkeys following intravenous infusion. The comprehensive nonclinical evaluations of this study provide robust evidence for regulatory approval, in addition to addressing of key scientific and technical challenges in biosimilar development.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2025.1698727","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:44:00Z","timestamp":1766040240000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonclinical evaluation of HS630, a proposed biosimilar of trastuzumab emtansine: affinity, pharmacokinetics, and immunogenicity"],"prefix":"10.3389","volume":"16","author":[{"given":"Hui","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinjing","family":"Che","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/bcr3621","article-title":"Trastuzumab emtansine: mechanisms of action and drug resistance","volume":"16","author":"Barok","year":"2014","journal-title":"Breast Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1016\/j.xphs.2023.09.007","article-title":"CMC regulatory considerations for antibody-drug conjugates","volume":"112","author":"Bechtold-Peters","year":"2023","journal-title":"J. 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