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Development of a TCR multimer with high avidity for detecting a naturally presented tumor-associated antigen on osteosarcoma cells.

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Development of a TCR multimer with high avidity for detecting a naturally presented tumor-associated antigen on osteosarcoma cells.

Cancer Sci. 2018 Oct 30;:

Authors: Watanabe K, Tsukahara T, Toji S, Saitoh S, Hirohashi Y, Nakatsugawa M, Kubo T, Kanaseki T, Kameshima H, Terui T, Sato N, Torigoe T

Abstract
For the efficacy of peptide vaccination immunotherapy for patients with cancer, endogenous expression of the target peptide/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 TAA with high avidity. In this study, we developed two soluble TCR-multimers that were each directed to tumor-associated antigens (TAAs), survivin2B 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 manner. 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. This article is protected by copyright. All rights reserved.

PMID: 30375705 [PubMed - as supplied by publisher]



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