Cancer Immunology, Immunotherapy

, Volume 53, Issue 4, pp 345–357

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

  • Kimberlyn F. Card
  • Shari A. Price-Schiavi
  • Bai Liu
  • Elizabeth Thomson
  • Esperanza Nieves
  • Heather Belmont
  • Janette Builes
  • Jin-an Jiao
  • Javier Hernandez
  • Jon Weidanz
  • Linda Sherman
  • John L. Francis
  • Ali Amirkhosravi
  • Hing C. Wong
Original Article

DOI: 10.1007/s00262-003-0450-3

Cite this article as:
Card, K.F., Price-Schiavi, S.A., Liu, B. et al. Cancer Immunol Immunother (2004) 53: 345. doi:10.1007/s00262-003-0450-3

Abstract

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.

Keywords

T cell receptorsTumor immunityMolecular biologyCytokines

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Kimberlyn F. Card
    • 1
  • Shari A. Price-Schiavi
    • 1
  • Bai Liu
    • 1
  • Elizabeth Thomson
    • 1
  • Esperanza Nieves
    • 2
  • Heather Belmont
    • 1
  • Janette Builes
    • 1
  • Jin-an Jiao
    • 6
  • Javier Hernandez
    • 3
  • Jon Weidanz
    • 4
  • Linda Sherman
    • 3
  • John L. Francis
    • 5
  • Ali Amirkhosravi
    • 5
  • Hing C. Wong
    • 1
  1. 1.Altor BioScience CorporationMiramarUSA
  2. 2.Dade-Behring CorporationNewarkUSA
  3. 3.The Scripps Research InstituteLa JollaUSA
  4. 4.Department of Pharmaceutical Sciences, School of PharmacyTexas Tech UniversityAmarilloUSA
  5. 5.Florida Hospital Cancer InstituteOrlandoUSA
  6. 6.Hematech LLCSioux FallsUSA