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

Abstract

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.

• Authors: M J Litton, M Dohlsten, J Hansson, A Rosendahl, L Ohlsson, T Kalland, J Andersson, U Andersson
• Journal: The American journal of pathology (Am J Pathol) Vol. 150 Issue 5 Pg. 1607-18 (May 1997) ISSN: 0002-9440 [Print] United States
• PMID: 9137087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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