Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells. Issue 1 (1st December 2018)

• Record Type: Journal Article
• Authors: Watanabe, Kazue; Tsukahara, Tomohide; Toji, Shingo; Saitoh, Shogo; Hirohashi, Yoshihiko; Nakatsugawa, Munehide; Kubo, Terufumi; Kanaseki, Takayuki; Kameshima, Hidekazu; Terui, Takeshi; Sato, Noriyuki; Torigoe, Toshihiko
• Is Part Of: Cancer science. Volume 110:Issue 1(2019)
• Page Start: 40
• Page End: 51
• Publication Date: 2018-12-01
• Subjects: HLA‐A24 -- multimer -- PBF -- survivin -- T‐cell receptor; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13854
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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. Abstract : We successfully generated TCR‐multimers reacting with HLA/TAA‐derived peptides, HLA‐A24/SVN‐2B peptide and HLA‐A24/PBF peptide complexes. PBF TCR‐multimer with high avidity could react with a naturally presented PBF peptide on osteosarcoma cell lines. TCR‐multimer might be useful for the detection of target antigens in immunotherapy.