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

Cancer Sci. 2019 Jan;110(1):40-51. doi: 10.1111/cas.13854. Epub 2018 Dec 1.


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.

Keywords: HLA-A24; PBF; T-cell receptor; multimer; survivin.

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Bone Neoplasms / immunology*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / therapy
  • Cell Line
  • Cell Line, Tumor
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • HLA-A24 Antigen / immunology
  • HLA-A24 Antigen / metabolism
  • Humans
  • Immunotherapy / methods
  • Osteosarcoma / immunology*
  • Osteosarcoma / metabolism
  • Osteosarcoma / therapy
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Survivin / immunology
  • Survivin / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism


  • Antigens, Neoplasm
  • BIRC5 protein, human
  • DNA-Binding Proteins
  • HLA-A24 Antigen
  • Peptides
  • Receptors, Antigen, T-Cell
  • Survivin