Radionuclide Therapy of HER2-Expressing Xenografts Using [<sup>177</sup>Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab
ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule Z<sub>HER2:2891</sub>, which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to Z<sub>HER2:2891</sub&...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/9/2409 |
| Summary: | ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule Z<sub>HER2:2891</sub>, which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to Z<sub>HER2:2891</sub> to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide <sup>177</sup>Lu using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [<sup>177</sup>Lu]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [<sup>177</sup>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 [<sup>177</sup>Lu]Lu-ABY-027 in tumors. Mice were treated with [<sup>177</sup>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 [<sup>177</sup>Lu]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [<sup>177</sup>Lu]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [<sup>177</sup>Lu]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors. |
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| ISSN: | 2072-6694 |