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Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells

For efficacy of peptide vaccination immunotherapy for patients with cancer, endogenous expression of the target peptide/human leukocyte antigen (HLA) on cancer cells is required. However, it is difficult to evaluate the expression status of a peptide/HLA complex because of the lack of a soluble T‐ce...

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Autores principales: Watanabe, Kazue, Tsukahara, Tomohide, Toji, Shingo, Saitoh, Shogo, Hirohashi, Yoshihiko, Nakatsugawa, Munehide, Kubo, Terufumi, Kanaseki, Takayuki, Kameshima, Hidekazu, Terui, Takeshi, Sato, Noriyuki, Torigoe, Toshihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317924/
https://www.ncbi.nlm.nih.gov/pubmed/30375705
http://dx.doi.org/10.1111/cas.13854
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author Watanabe, Kazue
Tsukahara, Tomohide
Toji, Shingo
Saitoh, Shogo
Hirohashi, Yoshihiko
Nakatsugawa, Munehide
Kubo, Terufumi
Kanaseki, Takayuki
Kameshima, Hidekazu
Terui, Takeshi
Sato, Noriyuki
Torigoe, Toshihiko
author_facet Watanabe, Kazue
Tsukahara, Tomohide
Toji, Shingo
Saitoh, Shogo
Hirohashi, Yoshihiko
Nakatsugawa, Munehide
Kubo, Terufumi
Kanaseki, Takayuki
Kameshima, Hidekazu
Terui, Takeshi
Sato, Noriyuki
Torigoe, Toshihiko
author_sort Watanabe, Kazue
collection PubMed
description For efficacy of peptide vaccination immunotherapy for patients with cancer, endogenous expression of the target peptide/human leukocyte antigen (HLA) on cancer cells is required. However, it is difficult to evaluate the expression status of a peptide/HLA complex because of the lack of a soluble T‐cell receptor (TCR) that reacts with tumor‐associated antigen (TAA) with high avidity. In the present study, we developed two soluble TCR‐multimers that were each directed to TAA, survivin‐2B (SVN‐2B) and PBF in the context of HLA‐A24 (SVN‐2B TCR‐multimer and PBF TCR‐multimer, respectively), from CTL clones that were established from peptide‐vaccinated patients. Both TCR multimers could recognize cognate peptide‐pulsed antigen‐presenting cells, C1R‐A24 cells, in a CD8‐independent method. Moreover, the PBF TCR‐multimer successfully recognized a PBF peptide naturally presented on HLA‐A24(+) PBF (+) osteosarcoma cells. Taken together, the results indicated that a TCR‐multimer might be useful for detection of a TAA‐derived peptide presented by HLA in patients receiving immunotherapy.
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spelling pubmed-63179242019-01-08 Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells Watanabe, Kazue Tsukahara, Tomohide Toji, Shingo Saitoh, Shogo Hirohashi, Yoshihiko Nakatsugawa, Munehide Kubo, Terufumi Kanaseki, Takayuki Kameshima, Hidekazu Terui, Takeshi Sato, Noriyuki Torigoe, Toshihiko Cancer Sci Original Articles For efficacy of peptide vaccination immunotherapy for patients with cancer, endogenous expression of the target peptide/human leukocyte antigen (HLA) on cancer cells is required. However, it is difficult to evaluate the expression status of a peptide/HLA complex because of the lack of a soluble T‐cell receptor (TCR) that reacts with tumor‐associated antigen (TAA) with high avidity. In the present study, we developed two soluble TCR‐multimers that were each directed to TAA, survivin‐2B (SVN‐2B) and PBF in the context of HLA‐A24 (SVN‐2B TCR‐multimer and PBF TCR‐multimer, respectively), from CTL clones that were established from peptide‐vaccinated patients. Both TCR multimers could recognize cognate peptide‐pulsed antigen‐presenting cells, C1R‐A24 cells, in a CD8‐independent method. Moreover, the PBF TCR‐multimer successfully recognized a PBF peptide naturally presented on HLA‐A24(+) PBF (+) osteosarcoma cells. Taken together, the results indicated that a TCR‐multimer might be useful for detection of a TAA‐derived peptide presented by HLA in patients receiving immunotherapy. John Wiley and Sons Inc. 2018-12-01 2019-01 /pmc/articles/PMC6317924/ /pubmed/30375705 http://dx.doi.org/10.1111/cas.13854 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Watanabe, Kazue
Tsukahara, Tomohide
Toji, Shingo
Saitoh, Shogo
Hirohashi, Yoshihiko
Nakatsugawa, Munehide
Kubo, Terufumi
Kanaseki, Takayuki
Kameshima, Hidekazu
Terui, Takeshi
Sato, Noriyuki
Torigoe, Toshihiko
Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title_full Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title_fullStr Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title_full_unstemmed Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title_short Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
title_sort development of a t‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317924/
https://www.ncbi.nlm.nih.gov/pubmed/30375705
http://dx.doi.org/10.1111/cas.13854
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