Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery
Abstract This study presents a novel approach targeting CD155, an overexpressed protein in lung adenocarcinoma (LUAD), using nanobodies with exceptional precision and efficacy. The significant upregulation of CD155 in LUAD, associated with poor patient outcomes, highlights its potential as a therape...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02301-z |
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| author | Kyunghee Noh Soyeon Yi Hyeran Kim Jieun Lee Suhyeon Kim Wonbeak Yoo Eunkyeong Jung Jinsol Choi Hwangseo Park Seungha Hwang Jin Young Kang Kwang-Hyun Park Heewon Park Yong-kyu Lee Eun-Kyung Lim Taejoon Kang Juyeon Jung |
| author_facet | Kyunghee Noh Soyeon Yi Hyeran Kim Jieun Lee Suhyeon Kim Wonbeak Yoo Eunkyeong Jung Jinsol Choi Hwangseo Park Seungha Hwang Jin Young Kang Kwang-Hyun Park Heewon Park Yong-kyu Lee Eun-Kyung Lim Taejoon Kang Juyeon Jung |
| author_sort | Kyunghee Noh |
| collection | DOAJ |
| description | Abstract This study presents a novel approach targeting CD155, an overexpressed protein in lung adenocarcinoma (LUAD), using nanobodies with exceptional precision and efficacy. The significant upregulation of CD155 in LUAD, associated with poor patient outcomes, highlights its potential as a therapeutic target. An anti-CD155 nanobody (A5 Nb) is developed that binds to CD155-positive lung cancer cells with high affinity (A5 Nb K d = 0.23 nM). The complementarity-determining region of A5 Nb forms hydrophobic interactions and hydrogen bonds with CD155, promoting selective binding and stabilization of A5 Nb-CD155 complex. This interaction inhibits focal adhesion signaling by downregulating paxillin (PXN), leading to a >50% reduction in cell migration. Additionally, A5 Nb conjugated to liposomes loaded with doxorubicin (A5-LNP-DOX) demonstrates a 2- to 3-fold increase in uptake and cytotoxicity in CD155-positive A549 cells, suggesting its potential as a targeted drug delivery system. Therapeutic efficacy was further validated in both lung orthotopic mouse models and lung cancer organoid xenografts, where A5-LNP-DOX exhibited robust antitumor effects and selective targeting. The CD155-PXN axis emerges as a clinically relevant target, correlating with poor outcomes in patients with lung cancer. This study highlights the therapeutic potential of A5 nanobodies in targeting CD155-overexpressing lung cancer cells and offers insights for future developments in lung cancer therapeutics. |
| format | Article |
| id | doaj-art-90d2ea50a93f4e4e82f3b902df276c8b |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-90d2ea50a93f4e4e82f3b902df276c8b2025-08-20T03:41:57ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-0110111510.1038/s41392-025-02301-zTargeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug deliveryKyunghee Noh0Soyeon Yi1Hyeran Kim2Jieun Lee3Suhyeon Kim4Wonbeak Yoo5Eunkyeong Jung6Jinsol Choi7Hwangseo Park8Seungha Hwang9Jin Young Kang10Kwang-Hyun Park11Heewon Park12Yong-kyu Lee13Eun-Kyung Lim14Taejoon Kang15Juyeon Jung16Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Deparment of Bioscience and Biotechnology, Sejong UniversityDepartment of Chemistry, Korea Advanced Institute of Science and Technology (KAIST)Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST)Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST)Department of Chemical and Biological Engineering, Korea National University of TransportationBionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Abstract This study presents a novel approach targeting CD155, an overexpressed protein in lung adenocarcinoma (LUAD), using nanobodies with exceptional precision and efficacy. The significant upregulation of CD155 in LUAD, associated with poor patient outcomes, highlights its potential as a therapeutic target. An anti-CD155 nanobody (A5 Nb) is developed that binds to CD155-positive lung cancer cells with high affinity (A5 Nb K d = 0.23 nM). The complementarity-determining region of A5 Nb forms hydrophobic interactions and hydrogen bonds with CD155, promoting selective binding and stabilization of A5 Nb-CD155 complex. This interaction inhibits focal adhesion signaling by downregulating paxillin (PXN), leading to a >50% reduction in cell migration. Additionally, A5 Nb conjugated to liposomes loaded with doxorubicin (A5-LNP-DOX) demonstrates a 2- to 3-fold increase in uptake and cytotoxicity in CD155-positive A549 cells, suggesting its potential as a targeted drug delivery system. Therapeutic efficacy was further validated in both lung orthotopic mouse models and lung cancer organoid xenografts, where A5-LNP-DOX exhibited robust antitumor effects and selective targeting. The CD155-PXN axis emerges as a clinically relevant target, correlating with poor outcomes in patients with lung cancer. This study highlights the therapeutic potential of A5 nanobodies in targeting CD155-overexpressing lung cancer cells and offers insights for future developments in lung cancer therapeutics.https://doi.org/10.1038/s41392-025-02301-z |
| spellingShingle | Kyunghee Noh Soyeon Yi Hyeran Kim Jieun Lee Suhyeon Kim Wonbeak Yoo Eunkyeong Jung Jinsol Choi Hwangseo Park Seungha Hwang Jin Young Kang Kwang-Hyun Park Heewon Park Yong-kyu Lee Eun-Kyung Lim Taejoon Kang Juyeon Jung Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery Signal Transduction and Targeted Therapy |
| title | Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery |
| title_full | Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery |
| title_fullStr | Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery |
| title_full_unstemmed | Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery |
| title_short | Targeting CD155 in lung adenocarcinoma: A5 nanobody-based therapeutics for precision treatment and enhanced drug delivery |
| title_sort | targeting cd155 in lung adenocarcinoma a5 nanobody based therapeutics for precision treatment and enhanced drug delivery |
| url | https://doi.org/10.1038/s41392-025-02301-z |
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