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Tumor-reactive superantigens suppress tumor growth in humanized SCID mice.

Abstract
Superantigens are extremely potent activators of T lymphocytes. To develop a tumor-reactive superantigen for cancer therapy, we made a recombinant fusion protein of the superantigen staphylococcal enterotoxin A (SEA) and the Fab region of the C242 monoclonal antibody (C242Fab-SEA), which recognize human colon carcinoma cells. The therapeutic effect of C242Fab-SEA on colon-cancer growth was examined in lymphocyte-engrafted humanized SCID mice bearing intraperitoneally growing Colo205 colon carcinomas. i.v. injections of C242Fab-SEA significantly inhibited tumor growth. The anti-tumor effect required the presence of human T cells in the SCID mice. Optimal therapeutic effects were seen with C242Fab-SEA, but not with C242Fab fragment or SEA alone, demonstrating that both entities of the fusion protein were required. C242Fab-SEA-treated tumors showed a massive infiltration of T cells in the tumor parenchyme, and was accompanied by enhanced expression of ICAM-I and HLA-DR on the tumor cells. The results demonstrate that Fab-SEA fusion proteins convey superantigenicity on tumor cells which evoke T-cell-dependent suppression of tumor growth.
AuthorsP A Lando, M Dohlsten, L Ohlsson, T Kalland
JournalInternational journal of cancer (Int J Cancer) Vol. 62 Issue 4 Pg. 466-71 (Aug 09 1995) ISSN: 0020-7136 [Print] United States
PMID7635573 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Enterotoxins
  • HLA-DR Antigens
  • Immunoglobulin Fab Fragments
  • Recombinant Fusion Proteins
  • Superantigens
  • Intercellular Adhesion Molecule-1
  • enterotoxin A, Staphylococcal
Topics
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Colonic Neoplasms (immunology, metabolism, therapy)
  • Enterotoxins (therapeutic use)
  • Female
  • HLA-DR Antigens (metabolism)
  • Humans
  • Immunoglobulin Fab Fragments (immunology, therapeutic use)
  • Intercellular Adhesion Molecule-1 (metabolism)
  • Lymphocytes, Tumor-Infiltrating (immunology)
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Recombinant Fusion Proteins (therapeutic use)
  • Superantigens (therapeutic use)
  • T-Lymphocytes (immunology)
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Up-Regulation

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