Open AccessDevelopment of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells
Author(s) -
Watanabe Kazue,
Tsukahara Tomohide,
Toji Shingo,
Saitoh Shogo,
Hirohashi Yoshihiko,
Nakatsugawa Munehide,
Kubo Terufumi,
Kanaseki Takayuki,
Kameshima Hidekazu,
Terui Takeshi,
Sato Noriyuki,
Torigoe Toshihiko
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13854
Subject(s) - t cell receptor , avidity , antigen , ctl* , cancer immunotherapy , human leukocyte antigen , immunotherapy , peptide , immunology , survivin , t cell , cancer research , context (archaeology) , biology , medicine , cancer , immune system , cd8 , biochemistry , paleontology
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 CD 8‐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.