Radionuclide Therapy of HER2-Expressing Xenografts Using [177Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab

Radionuclide Therapy of HER2-Expressing Xenografts Using [177Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab

Bibliographische Detailangaben
Parent link:Cancers.— .— Basel: MDPI AG
Vol. 15 - iss. 9.— 2023.— Article number 2409, P. 1-15
Körperschaft: National Research Tomsk Polytechnic University
Weitere Verfasser: Liu Yongsheng, Xu Tianqi, Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Loftenius Annika, Bodenko V. V. Vitalina Vasiljevna, Orlova A. M. Anna Markovna, Frejd Y. F. Fredrik, Tolmachev V. M. Vladimir Maksimilianovich
Zusammenfassung:ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the secondgeneration Affibody molecule ZHER2:2891, which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to ZHER2:2891 to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide 177Lu using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [177Lu]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [177Lu]Lu-ABY-027 and the HER2-targeting antibody trastuzumab could enhance this effect. Balb/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts were used as in vivo models. A pre-injection of trastuzumab did not reduce the uptake of [177Lu]Lu-ABY-027 in tumors. Mice were treated with [177Lu]Lu-ABY-027 or trastuzumab as monotherapies and a combination of these therapies. Mice treated with vehicle or unlabeled ABY-027 were used as controls. Targeted monotherapy using [177Lu]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [177Lu]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [177Lu]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors.
Текстовый файл
Sprache:Englisch
Veröffentlicht: 2023
Schlagworte:
radionuclide therapy
Affibody molecule
HER2
lutetium-177
труды учёных ТПУ
электронный ресурс
Online-Zugang:https://doi.org/10.3390/cancers15092409
Format: Elektronisch Buchkapitel
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=671222

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