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Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival

Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long‐term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor‐specific CTLs could play a role in long‐term survival (5 years or longer) in patients with recurrence...

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Autores principales: Takagi‐Maeda, Sayaka, Yajima, Satoshi, Suzuki, Takashi, Usami, Katsuaki, Takahashi, Nobuaki, Niwa, Rinpei, Shimada, Hideaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207364/
https://www.ncbi.nlm.nih.gov/pubmed/35348270
http://dx.doi.org/10.1111/cas.15350
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author Takagi‐Maeda, Sayaka
Yajima, Satoshi
Suzuki, Takashi
Usami, Katsuaki
Takahashi, Nobuaki
Niwa, Rinpei
Shimada, Hideaki
author_facet Takagi‐Maeda, Sayaka
Yajima, Satoshi
Suzuki, Takashi
Usami, Katsuaki
Takahashi, Nobuaki
Niwa, Rinpei
Shimada, Hideaki
author_sort Takagi‐Maeda, Sayaka
collection PubMed
description Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long‐term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor‐specific CTLs could play a role in long‐term survival (5 years or longer) in patients with recurrence and/or distant metastases. Therefore, we aimed to obtain Abs that specifically bind to cancer cells by using serum samples from patients with a good prognosis. A phage library was prepared using PBMC mRNA of the patients, and cell panning was carried out using an esophageal cancer cell line. Results showed the presence of an epidermal growth factor receptor (EGFR) Ab, KT112, that specifically bound to the cancer cell line. Notably, KT112 bound to only EGFR‐positive cancer cells but failed to bind to normal esophageal cells. Furthermore, KT112 was characterized by responses to EGFR expressed on cancer cells but not to the recombinant extracellular domain of EGFR. Immunohistochemical analysis showed that KT112 reacted with 17.4% of esophageal squamous cell carcinoma tissue but not with any other cancer or normal tissue, suggesting that the Ab recognizes cancer‐specific forms of EGFR and might have contributed to tumor suppression in patients with esophageal cancer. Furthermore, because of its high cancer specificity, KT112 could be a promising therapeutic option (e.g., in Ab‐drug conjugates) for esophageal cancer.
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spelling pubmed-92073642022-06-27 Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival Takagi‐Maeda, Sayaka Yajima, Satoshi Suzuki, Takashi Usami, Katsuaki Takahashi, Nobuaki Niwa, Rinpei Shimada, Hideaki Cancer Sci ORIGINAL ARTICLES Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long‐term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor‐specific CTLs could play a role in long‐term survival (5 years or longer) in patients with recurrence and/or distant metastases. Therefore, we aimed to obtain Abs that specifically bind to cancer cells by using serum samples from patients with a good prognosis. A phage library was prepared using PBMC mRNA of the patients, and cell panning was carried out using an esophageal cancer cell line. Results showed the presence of an epidermal growth factor receptor (EGFR) Ab, KT112, that specifically bound to the cancer cell line. Notably, KT112 bound to only EGFR‐positive cancer cells but failed to bind to normal esophageal cells. Furthermore, KT112 was characterized by responses to EGFR expressed on cancer cells but not to the recombinant extracellular domain of EGFR. Immunohistochemical analysis showed that KT112 reacted with 17.4% of esophageal squamous cell carcinoma tissue but not with any other cancer or normal tissue, suggesting that the Ab recognizes cancer‐specific forms of EGFR and might have contributed to tumor suppression in patients with esophageal cancer. Furthermore, because of its high cancer specificity, KT112 could be a promising therapeutic option (e.g., in Ab‐drug conjugates) for esophageal cancer. John Wiley and Sons Inc. 2022-04-18 2022-06 /pmc/articles/PMC9207364/ /pubmed/35348270 http://dx.doi.org/10.1111/cas.15350 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle ORIGINAL ARTICLES
Takagi‐Maeda, Sayaka
Yajima, Satoshi
Suzuki, Takashi
Usami, Katsuaki
Takahashi, Nobuaki
Niwa, Rinpei
Shimada, Hideaki
Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title_full Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title_fullStr Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title_full_unstemmed Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title_short Novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
title_sort novel cancer‐specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long‐term survival
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207364/
https://www.ncbi.nlm.nih.gov/pubmed/35348270
http://dx.doi.org/10.1111/cas.15350
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