Radionuclide Therapy of HER2-Expressing Xenografts Using [ 177 Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab.
In: Cancers, Jg. 15 (2023-05-01), Heft 9, S. 2409-2423
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Zugriff:
Simple Summary: Affibody molecules are artificial proteins that can recognize cancer-related molecular abnormalities in the living body. Clinical studies demonstrated that Affibody molecules can be successfully used for radionuclide diagnostics. Targeted radionuclide therapy selectively delivers cytotoxic radionuclides to malignant tumors, thus sparing normal tissues. For radionuclide therapy, Affibody molecules were re-engineered to decrease accumulation in the kidneys. This study has demonstrated that radionuclide therapy using re-engineered Affibody molecules increases the survival of immunodeficient mice bearing human tumors. The therapy was more efficient than the treatment with a monoclonal antibody, which is currently used in clinical practice. The best results were obtained when both the antibody and radiolabeled Affibody molecules were used simultaneously. This work provides a preclinical rationale for a potentially more efficient treatment in HER2-positive cancers. ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule Z HER2:2891 , which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to Z HER2:2891 to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide 177 Lu using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [ 177 Lu]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [ 177 Lu]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 [ 177 Lu]Lu-ABY-027 in tumors. Mice were treated with [ 177 Lu]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 [ 177 Lu]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [ 177 Lu]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [ 177 Lu]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors. [ABSTRACT FROM AUTHOR]
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Titel: |
Radionuclide Therapy of HER2-Expressing Xenografts Using [ 177 Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab.
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Autor/in / Beteiligte Person: | Liu, Yongsheng ; Xu, Tianqi ; Vorobyeva, Anzhelika ; Loftenius, Annika ; Bodenko, Vitalina ; Orlova, Anna ; Frejd, Fredrik Y. ; Tolmachev, Vladimir |
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Zeitschrift: | Cancers, Jg. 15 (2023-05-01), Heft 9, S. 2409-2423 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 2072-6694 (print) |
DOI: | 10.3390/cancers15092409 |
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