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A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells
Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CAD...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266846/ https://www.ncbi.nlm.nih.gov/pubmed/35805896 http://dx.doi.org/10.3390/ijms23136895 |
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author | Lee, Ji Hyun Kim, Ji Woong Yang, Ha Rim Song, Seong-Won Lee, Song-Jae Jeon, Yeongha Ju, Anna Lee, Narim Kim, Min-Gu Kim, Minjoo Hwang, Kyusang Yoon, Jin Hwan Shim, Hyunbo Lee, Sukmook |
author_facet | Lee, Ji Hyun Kim, Ji Woong Yang, Ha Rim Song, Seong-Won Lee, Song-Jae Jeon, Yeongha Ju, Anna Lee, Narim Kim, Min-Gu Kim, Minjoo Hwang, Kyusang Yoon, Jin Hwan Shim, Hyunbo Lee, Sukmook |
author_sort | Lee, Ji Hyun |
collection | PubMed |
description | Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy. |
format | Online Article Text |
id | pubmed-9266846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92668462022-07-09 A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells Lee, Ji Hyun Kim, Ji Woong Yang, Ha Rim Song, Seong-Won Lee, Song-Jae Jeon, Yeongha Ju, Anna Lee, Narim Kim, Min-Gu Kim, Minjoo Hwang, Kyusang Yoon, Jin Hwan Shim, Hyunbo Lee, Sukmook Int J Mol Sci Article Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy. MDPI 2022-06-21 /pmc/articles/PMC9266846/ /pubmed/35805896 http://dx.doi.org/10.3390/ijms23136895 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Ji Hyun Kim, Ji Woong Yang, Ha Rim Song, Seong-Won Lee, Song-Jae Jeon, Yeongha Ju, Anna Lee, Narim Kim, Min-Gu Kim, Minjoo Hwang, Kyusang Yoon, Jin Hwan Shim, Hyunbo Lee, Sukmook A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title | A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title_full | A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title_fullStr | A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title_full_unstemmed | A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title_short | A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells |
title_sort | fully-human antibody specifically targeting a membrane-bound fragment of cadm1 potentiates the t cell-mediated death of human small-cell lung cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266846/ https://www.ncbi.nlm.nih.gov/pubmed/35805896 http://dx.doi.org/10.3390/ijms23136895 |
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