Tumor therapy with an antibody-targeted superantigen generates a dichotomy between local and systemic immune responses

Am J Pathol. 1997 May;150(5):1607-18.


Repeated injections of a fusion protein containing the superantigen staphylococcal enterotoxin A (SEA) combined with a Fab fragment of a tumor-specific antibody is a highly efficient immunotherapy for mice expressing lung melanoma micrometastasis. In the present study, the systemic and local immune responses generated by this therapy were analyzed at a cellular level. Two distinct but coupled immune reactions occurred after repeated therapy. Tumor necrosis factor and macrophage inflammatory protein-1 alpha and -1 beta were immediately synthesized, in the absence of T lymphocytes, at the local tumor site in the lung. This was followed by the induction of VCAM-1 adhesion molecule expression on pulmonary vascular endothelial cells. Concurrently, the early response in the spleen was characterized by the induction of selective T cells producing interleukin (IL)-2. The primed and expanded SEA-reactive V beta 3- and V beta 11-expressing T lymphocytes accumulated to the tumor area only after Fab-SEA therapy and were not present in the lung when SEA, Fab fragment, or recombinant IL-2 was injected. The tumor-infiltrating T cells produced large amounts of interferon-gamma, but no IL-2 or Th2 type of lymphokines were detected at the tumor site in the Fab-SEA-targeted antitumor immune response. These results emphasize the necessity to investigate several sites of antigen presentation to elucidate the effects of immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / metabolism
  • Antibodies, Neoplasm / pharmacology
  • Antibodies, Neoplasm / therapeutic use*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Movement
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Enterotoxins / immunology*
  • Enterotoxins / metabolism
  • Enterotoxins / pharmacology
  • Immunoglobulin Fab Fragments / pharmacology
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Immunotoxins / metabolism
  • Immunotoxins / pharmacology
  • Immunotoxins / therapeutic use*
  • Kinetics
  • Lung / immunology
  • Lung / metabolism
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology
  • Spleen / metabolism
  • Staphylococcus aureus / immunology*
  • Superantigens / immunology*
  • Superantigens / metabolism
  • Superantigens / pharmacology


  • Antibodies, Neoplasm
  • Cell Adhesion Molecules
  • Cytokines
  • Enterotoxins
  • Immunoglobulin Fab Fragments
  • Immunotoxins
  • Superantigens
  • enterotoxin A, Staphylococcal