Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein

Clin Immunol. 2006 Oct;121(1):29-39. doi: 10.1016/j.clim.2006.05.005. Epub 2006 Jun 30.


We previously have generated a single-chain T cell receptor-cytokine fusion protein (264scTCR/IL-2) comprising interleukin-2 genetically linked to a soluble HLA-A2.1-restricted TCR recognizing a peptide of human p53 protein. In this report, we show that 264scTCR/IL-2 inhibits the growth of primary tumors derived from the A375 (p53+/HLA-A2.1+) human melanoma and exhibits significantly better antitumor activity than recombinant human IL-2 alone. Moreover, treatment with 264scTCR/IL-2 results in tumor growth retardation in mice bearing large A375 tumors and other p53+/HLA-A2.1+ human tumors but does not affect tumor outgrowth of HLA-A2.1-negative tumors. This suggests that antigen targeting plays a substantial role in the efficacy of 264scTCR/IL-2 against p53+/HLA-A2+ tumors. Further, the antitumor activity of 264scTCR/IL-2 was found to be likely mediated by NK cell activation and tumor infiltration. A biologically active chimeric version of the molecule (c264scTCR/IL-2) also exhibits favorable pharmacokinetic properties required of a clinical candidate for this novel class of potent antitumor activities and targeted anticancer immunotherapeutics.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Female
  • HT29 Cells
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Interleukin-2 / therapeutic use*
  • Male
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use*
  • Solubility
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / immunology*
  • Tumor Suppressor Protein p53 / therapeutic use


  • Antineoplastic Agents
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53