A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy.
Hodgkin's lymphoma and anaplastic large cell lymphoma, especially relapsed or refractory diseases, could recently be cured by CD30-targeted immunotherapy. However, the CD30 antigen releases the soluble ectodomain of CD30, which might obscure the targeted therapy. Therefore, the membrane epitope...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0284708 |
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author | Thanida Chanpong Watee Seesuay Wararat Chiangjong Piamsiri Jiramornimit Sarinthip Preedagasamzin Korakot Atjanasuppat Bunyada Jittorntrum Somsak Prasongtanakij Supannikar Tawinwung Sulada Pukiat Chonticha Saisawang Suparerk Borwornpinyo Khanit Sa-Ngiamsuntorn Wanpen Chaichumpa Suradej Hongeng Usanarat Anurathapan |
author_facet | Thanida Chanpong Watee Seesuay Wararat Chiangjong Piamsiri Jiramornimit Sarinthip Preedagasamzin Korakot Atjanasuppat Bunyada Jittorntrum Somsak Prasongtanakij Supannikar Tawinwung Sulada Pukiat Chonticha Saisawang Suparerk Borwornpinyo Khanit Sa-Ngiamsuntorn Wanpen Chaichumpa Suradej Hongeng Usanarat Anurathapan |
author_sort | Thanida Chanpong |
collection | DOAJ |
description | Hodgkin's lymphoma and anaplastic large cell lymphoma, especially relapsed or refractory diseases, could recently be cured by CD30-targeted immunotherapy. However, the CD30 antigen releases the soluble ectodomain of CD30, which might obscure the targeted therapy. Therefore, the membrane epitope of CD30 (mCD30), left on the cancer cells, might be a prospective target for lymphoma treatment. The discovery of novel mCD30 monoclonal antibodies (mAbs) using phage technology yielded 59 potential human single-chain variable fragments (HuscFvs). Ten candidate HuscFv clones have been selected based on various methods, i.e., direct PCR, ELISA and western blot assays, and nucleotide sequencing techniques. Fortunately, only one potential HuscFv clone, clone #A4, was determined by the prediction of HuscFv-peptide molecular docking and the binding affinity test using isothermal titration calorimetry. Finally, we proved that the HuscFv #A4, which had a binding affinity (Kd) of 421e-9 ± 2.76e-6 M, might be the novel mCD30 mAb. We generated chimeric antigen receptor-modified T lymphocytes using HuscFv #A4 as an antigen detection part (anti-mCD30-H4CART). The cytotoxicity assay of anti-mCD30-H4CART cells showed significant eradication of the CD30-expressing cell line, K562 (p = 0.0378). We found a novel mCD30 HuscFv using human phage technology. We systematically examined and proved that our HuscFv #A4 could specifically eradicate CD30-expressing cancers. |
first_indexed | 2024-04-09T13:27:42Z |
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id | doaj.art-a23c118eba584c6781b4ea36f1f8aa2d |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-09T13:27:42Z |
publishDate | 2023-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-a23c118eba584c6781b4ea36f1f8aa2d2023-05-10T05:32:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01184e028470810.1371/journal.pone.0284708A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy.Thanida ChanpongWatee SeesuayWararat ChiangjongPiamsiri JiramornimitSarinthip PreedagasamzinKorakot AtjanasuppatBunyada JittorntrumSomsak PrasongtanakijSupannikar TawinwungSulada PukiatChonticha SaisawangSuparerk BorwornpinyoKhanit Sa-NgiamsuntornWanpen ChaichumpaSuradej HongengUsanarat AnurathapanHodgkin's lymphoma and anaplastic large cell lymphoma, especially relapsed or refractory diseases, could recently be cured by CD30-targeted immunotherapy. However, the CD30 antigen releases the soluble ectodomain of CD30, which might obscure the targeted therapy. Therefore, the membrane epitope of CD30 (mCD30), left on the cancer cells, might be a prospective target for lymphoma treatment. The discovery of novel mCD30 monoclonal antibodies (mAbs) using phage technology yielded 59 potential human single-chain variable fragments (HuscFvs). Ten candidate HuscFv clones have been selected based on various methods, i.e., direct PCR, ELISA and western blot assays, and nucleotide sequencing techniques. Fortunately, only one potential HuscFv clone, clone #A4, was determined by the prediction of HuscFv-peptide molecular docking and the binding affinity test using isothermal titration calorimetry. Finally, we proved that the HuscFv #A4, which had a binding affinity (Kd) of 421e-9 ± 2.76e-6 M, might be the novel mCD30 mAb. We generated chimeric antigen receptor-modified T lymphocytes using HuscFv #A4 as an antigen detection part (anti-mCD30-H4CART). The cytotoxicity assay of anti-mCD30-H4CART cells showed significant eradication of the CD30-expressing cell line, K562 (p = 0.0378). We found a novel mCD30 HuscFv using human phage technology. We systematically examined and proved that our HuscFv #A4 could specifically eradicate CD30-expressing cancers.https://doi.org/10.1371/journal.pone.0284708 |
spellingShingle | Thanida Chanpong Watee Seesuay Wararat Chiangjong Piamsiri Jiramornimit Sarinthip Preedagasamzin Korakot Atjanasuppat Bunyada Jittorntrum Somsak Prasongtanakij Supannikar Tawinwung Sulada Pukiat Chonticha Saisawang Suparerk Borwornpinyo Khanit Sa-Ngiamsuntorn Wanpen Chaichumpa Suradej Hongeng Usanarat Anurathapan A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. PLoS ONE |
title | A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. |
title_full | A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. |
title_fullStr | A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. |
title_full_unstemmed | A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. |
title_short | A novel anti-membrane CD30 single-chain variable fragment discovered from the human phage library: A potential targeted immunotherapy. |
title_sort | novel anti membrane cd30 single chain variable fragment discovered from the human phage library a potential targeted immunotherapy |
url | https://doi.org/10.1371/journal.pone.0284708 |
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