Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer

Decay-accelerating factor (CD55 or DAF) inhibits complement-dependent cytotoxicity. We determined that CD55 is overexpressed in 76.47% of human non-small cell lung cancer tissue specimens. We therefore developed a lutetium-177-labeled chimeric monoclonal antibody against CD55. CD55-specific single-c...

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Autores principales: Dho, So Hee, Kim, Soo Yong, Chung, Chaeuk, Cho, Eun Ha, Lee, So-Young, Kim, Ji Young, Kim, Lark Kyun, Min, Sung-Won, Lee, Jichul, Jung, Sung Hee, Lim, Jae Cheong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997699/
https://www.ncbi.nlm.nih.gov/pubmed/29895866
http://dx.doi.org/10.1038/s41598-018-27355-8
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author Dho, So Hee
Kim, Soo Yong
Chung, Chaeuk
Cho, Eun Ha
Lee, So-Young
Kim, Ji Young
Kim, Lark Kyun
Min, Sung-Won
Lee, Jichul
Jung, Sung Hee
Lim, Jae Cheong
author_facet Dho, So Hee
Kim, Soo Yong
Chung, Chaeuk
Cho, Eun Ha
Lee, So-Young
Kim, Ji Young
Kim, Lark Kyun
Min, Sung-Won
Lee, Jichul
Jung, Sung Hee
Lim, Jae Cheong
author_sort Dho, So Hee
collection PubMed
description Decay-accelerating factor (CD55 or DAF) inhibits complement-dependent cytotoxicity. We determined that CD55 is overexpressed in 76.47% of human non-small cell lung cancer tissue specimens. We therefore developed a lutetium-177-labeled chimeric monoclonal antibody against CD55. CD55-specific single-chain variable fragment (scFv) was selected from a naïve chicken scFv phage-display library, converted to IgG, and radiolabeled with lutetium-177 to generate a (177)Lu-anti-CD55 antibody. We then charaterized the biodistribution of this antibody in a mouse model of pleural metastatic lung cancer. The (177)Lu-anti-CD55 antibody was primarily retained in tumor tissue rather than normal tissue. Treatment of the mice with (177)Lu-anti-CD55 reduced the growth of lung tumors and improved median survival in vivo by two-fold compared to controls. Finally, (177)Lu-anti-CD55 also enhanced the antitumor activity of cisplatin both in vitro and in vivo. These data suggest (177)Lu-anti-CD55 antibody is a promising theranostic agent for pleural metastatic lung cancer.
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spelling pubmed-59976992018-06-21 Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer Dho, So Hee Kim, Soo Yong Chung, Chaeuk Cho, Eun Ha Lee, So-Young Kim, Ji Young Kim, Lark Kyun Min, Sung-Won Lee, Jichul Jung, Sung Hee Lim, Jae Cheong Sci Rep Article Decay-accelerating factor (CD55 or DAF) inhibits complement-dependent cytotoxicity. We determined that CD55 is overexpressed in 76.47% of human non-small cell lung cancer tissue specimens. We therefore developed a lutetium-177-labeled chimeric monoclonal antibody against CD55. CD55-specific single-chain variable fragment (scFv) was selected from a naïve chicken scFv phage-display library, converted to IgG, and radiolabeled with lutetium-177 to generate a (177)Lu-anti-CD55 antibody. We then charaterized the biodistribution of this antibody in a mouse model of pleural metastatic lung cancer. The (177)Lu-anti-CD55 antibody was primarily retained in tumor tissue rather than normal tissue. Treatment of the mice with (177)Lu-anti-CD55 reduced the growth of lung tumors and improved median survival in vivo by two-fold compared to controls. Finally, (177)Lu-anti-CD55 also enhanced the antitumor activity of cisplatin both in vitro and in vivo. These data suggest (177)Lu-anti-CD55 antibody is a promising theranostic agent for pleural metastatic lung cancer. Nature Publishing Group UK 2018-06-12 /pmc/articles/PMC5997699/ /pubmed/29895866 http://dx.doi.org/10.1038/s41598-018-27355-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dho, So Hee
Kim, Soo Yong
Chung, Chaeuk
Cho, Eun Ha
Lee, So-Young
Kim, Ji Young
Kim, Lark Kyun
Min, Sung-Won
Lee, Jichul
Jung, Sung Hee
Lim, Jae Cheong
Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title_full Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title_fullStr Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title_full_unstemmed Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title_short Development of a radionuclide-labeled monoclonal anti-CD55 antibody with theranostic potential in pleural metastatic lung cancer
title_sort development of a radionuclide-labeled monoclonal anti-cd55 antibody with theranostic potential in pleural metastatic lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997699/
https://www.ncbi.nlm.nih.gov/pubmed/29895866
http://dx.doi.org/10.1038/s41598-018-27355-8
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