Original Article

Cancer Immunology, Immunotherapy

, Volume 53, Issue 4, pp 345-357

First online:

A soluble single-chain T-cell receptor IL-2 fusion protein retains MHC-restricted peptide specificity and IL-2 bioactivity

  • Kimberlyn F. CardAffiliated withAltor BioScience Corporation
  • , Shari A. Price-SchiaviAffiliated withAltor BioScience Corporation
  • , Bai LiuAffiliated withAltor BioScience Corporation
  • , Elizabeth ThomsonAffiliated withAltor BioScience Corporation
  • , Esperanza NievesAffiliated withDade-Behring Corporation
  • , Heather BelmontAffiliated withAltor BioScience Corporation
  • , Janette BuilesAffiliated withAltor BioScience Corporation
  • , Jin-an JiaoAffiliated withHematech LLC
  • , Javier HernandezAffiliated withThe Scripps Research Institute
    • , Jon WeidanzAffiliated withDepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University
    • , Linda ShermanAffiliated withThe Scripps Research Institute
    • , John L. FrancisAffiliated withFlorida Hospital Cancer Institute
    • , Ali AmirkhosraviAffiliated withFlorida Hospital Cancer Institute
    • , Hing C. WongAffiliated withAltor BioScience Corporation Email author 

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Antibody-based targeted immunotherapy has shown promise as an approach to treat cancer. However, many known tumor-associated antigens are not expressed as integral membrane proteins and cannot be utilized as targets for antibody-based therapeutics. In order to expand the limited target range of antibodies, we have constructed a soluble single-chain T-cell receptor (TCR) fusion protein designated 264scTCR/IL-2. This fusion protein is comprised of a three-domain HLA-A2-restricted TCR specific for a peptide epitope of the human p53 tumor suppressor protein, which is overexpressed in a broad range of human malignancies. The 264scTCR/IL-2 fusion protein has been expressed at high levels in mammalian cells, and milligram quantities have been purified. MHC-restricted antigen-specific binding properties are maintained in the single-chain, three-domain TCR portion of the fusion protein, and the IL-2 portion retains bioactivity similar to that of free recombinant IL-2. Moreover, this fusion protein is capable of conjugating target and effector cells, remains intact in the blood and substantially increases the half life of the IL-2 portion of the molecule. Finally, the 264scTCR/IL-2 fusion protein can be used to stain tumor cells and is capable of reducing lung metastases in an experimental model of metastasis. Thus, TCR-based fusion proteins may provide a novel class of targeted immunotherapeutics for cancer.


T cell receptors Tumor immunity Molecular biology Cytokines