Preclinical Evaluation of HER2-Targeting DARPin G3: Impact of Albumin-Binding Domain (ABD) Fusion
| Parent link: | International Journal of Molecular Sciences.— .— Basel: MDPI AG Vol. 25, iss. 8.— 2024.— Article number 4246, 17 p. |
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| مؤلفون آخرون: | , , , , , , , , , , |
| الملخص: | Title screen Designed ankyrin repeat protein (DARPin) G3 is an engineered scaffold protein. This small (14.5 kDa) targeting protein binds with high affinity to human epidermal growth factor receptor 2 (HER2). HER2 is overexpressed in several cancers. The use of the DARPin G3 for radionuclide therapy is complicated by its high renal reabsorption after clearance via the glomeruli. We tested the hypothesis that a fusion of the DARPin G3 with an albumin-binding domain (ABD) would prevent rapid renal excretion and high renal reabsorption resulting in better tumour targeting. Two fusion proteins were produced, one with the ABD at the C-terminus (G3-ABD) and another at the N-terminus (ABD-G3). Both variants were labelled with 177Lu. The binding properties of the novel constructs were evaluated in vitro and their biodistribution was compared in mice with implanted human HER2-expressing tumours. Fusion with the ABD increased the retention time of both constructs in blood compared with the non-ABD-fused control. The effect of fusion with the ABD depended strongly on the order of the domains in the constructs, resulting in appreciably better targeting properties of [177Lu]Lu-G3-ABD. Our data suggest that the order of domains is critical for the design of targeting constructs based on scaffold proteins. Текстовый файл |
| اللغة: | الإنجليزية |
| منشور في: |
2024
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://doi.org/10.3390/ijms25084246 |
| التنسيق: | الكتروني فصل الكتاب |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=672867 |
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| 200 | 1 | |a Preclinical Evaluation of HER2-Targeting DARPin G3: Impact of Albumin-Binding Domain (ABD) Fusion |f S. M. Deyev, M. Oroujeni, J. Garousi [et al.] | |
| 203 | |a Текст |b визуальный |c электронный | ||
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| 300 | |a Title screen | ||
| 320 | |a References: 45 tit. | ||
| 330 | |a Designed ankyrin repeat protein (DARPin) G3 is an engineered scaffold protein. This small (14.5 kDa) targeting protein binds with high affinity to human epidermal growth factor receptor 2 (HER2). HER2 is overexpressed in several cancers. The use of the DARPin G3 for radionuclide therapy is complicated by its high renal reabsorption after clearance via the glomeruli. We tested the hypothesis that a fusion of the DARPin G3 with an albumin-binding domain (ABD) would prevent rapid renal excretion and high renal reabsorption resulting in better tumour targeting. Two fusion proteins were produced, one with the ABD at the C-terminus (G3-ABD) and another at the N-terminus (ABD-G3). Both variants were labelled with 177Lu. The binding properties of the novel constructs were evaluated in vitro and their biodistribution was compared in mice with implanted human HER2-expressing tumours. Fusion with the ABD increased the retention time of both constructs in blood compared with the non-ABD-fused control. The effect of fusion with the ABD depended strongly on the order of the domains in the constructs, resulting in appreciably better targeting properties of [177Lu]Lu-G3-ABD. Our data suggest that the order of domains is critical for the design of targeting constructs based on scaffold proteins. | ||
| 336 | |a Текстовый файл | ||
| 461 | 1 | |t International Journal of Molecular Sciences |n MDPI AG |c Basel | |
| 463 | 1 | |t Vol. 25, iss. 8 |v Article number 4246, 17 p. |d 2024 | |
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a DARPin G3 | |
| 610 | 1 | |a albumin-binding domain (ABD) | |
| 610 | 1 | |a HER2 | |
| 610 | 1 | |a SKOV-3 xenograft | |
| 610 | 1 | |a Lutetium-177 (177Lu) | |
| 610 | 1 | |a SPECT imaging | |
| 701 | 1 | |a Deev |b S. M. |c biologist |c Leading Researcher, Tomsk Polytechnic University, Doctor of Biological Sciences |f 1951- |g Sergey Mikhaylovich |9 20959 | |
| 701 | 1 | |a Oroujeni |b M. |g Maryam | |
| 701 | 1 | |a Garousi |b J. |g Javad | |
| 701 | 1 | |a Gräslund |b T. |g Torbjörn | |
| 701 | 1 | |a Li |b R. |g Ruonan | |
| 701 | 1 | |a Rosly |b A. H. B. |g Alia Hani Binti | |
| 701 | 1 | |a Orlova |b A. M. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1960- |g Anna Markovna |9 22212 | |
| 701 | 1 | |a Konovalova |b E. V. |c specialist in the field of chemical technology and biotechnology |c engineer at Tomsk Polytechnic University |f 1985- |g Elena Valerjevna |9 88562 | |
| 701 | 1 | |a Shulga (Schulga) |b A. A. |c biologist |c Researcher, Tomsk Polytechnic University, Candidate of Biological Sciences |f 1960- |g Aleksey Anatolievich |9 22432 | |
| 701 | 1 | |a Vorobjeva (Vorobyeva) |b A. G. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1990- |g Anzhelika Grigorjevna |9 22214 | |
| 701 | 1 | |a Tolmachev |b V. M. |c specialist in the field of medical technology |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D |f 1961- |g Vladimir Maksimilianovich |9 22210 | |
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