T-cell immunotherapy for human MK-1-expressing tumors using a fusion protein of the superantigen SEA and anti-MK-1 scFv antibody

Aruto Ueno, Fumiko Arakawa, Hironori Abe, Hisanobu Matsumoto, Toshio Kudo, Ryutaro Asano, Kohei Tsumoto, Izumi Kumagai, Motomu Kuroki, Masahide Kuroki

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we constructed a recombinant fusion protein of SEA and the single-chain variable fragment (scFv) of the FU-MK-1 antibody, which recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas. Materials and Methods: We employed recombinant DNA techniques to fuse recombinant mutant SEA to an scFv antibody derived from FU-MK-1 and the resulting fusion protein (SEA/FUscFv) was produced by a bacterial expression system, purified with a metal-affinity column, and characterized for its MK-1-binding specificity and its antitumor activity. Results: The SEA/FUscFv fusion protein retained the reactivity with MK-1-expressing tumor cells, introduced a specific cytotoxicity of lymphokine-activated killer T-cells to the tumor cells, and consequently suppressed the tumor growth in a SCID mouse xenograft model. Conclusion: This genetically engineered SEA/FUscFv fusion protein may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalAnticancer research
Volume22
Issue number2 A
Publication statusPublished - 2002

Keywords

  • Fusion protein
  • Immunotherapy
  • SEA
  • Superantigen
  • scFv

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ueno, A., Arakawa, F., Abe, H., Matsumoto, H., Kudo, T., Asano, R., Tsumoto, K., Kumagai, I., Kuroki, M., & Kuroki, M. (2002). T-cell immunotherapy for human MK-1-expressing tumors using a fusion protein of the superantigen SEA and anti-MK-1 scFv antibody. Anticancer research, 22(2 A), 769-776.