Immunotherapy of human colon cancer by antibody-targeted superantigens.

Abstract	T lymphocytes generally fail to recognize human colon carcinomas, suggesting that the tumour is beyond reach of immunotherapy. Bacterial superantigens are the most potent known activators of human T lymphocytes and induce T cell cytotoxicity and cytokine production. In order to develop a T-cell-based therapy for colon cancer, the superantigen staphylococcal enterotoxin A (SEA) was given tumour reactivity by genetic fusion with a Fab fragment of the monoclonal antibody C242 reacting with human colon carcinomas. The C242Fab-SEA fusion protein targeted SEA-reactive T cells against MHC-class-II-negative human colon carcinoma cells in vitro at nanomolar concentrations. Treatment of disseminated human colon carcinomas growing in humanized SCID mice resulted in marked inhibition of tumour growth and the apparent cure of the animals. Therapeutic efficiency was dependent on the tumour specificity of the fusion protein and human T cells. Immunohistochemistry demonstrated massive infiltration of human T cells in C242Fab-SEA-treated tumours. The results merit further evaluation of C242Fab-SEA fusion proteins as immunotherapy in patients suffering from colon carcinoma.
Authors	M Dohlsten, P A Lando, P Björk, L Abrahmsén, L Ohlsson, P Lind, T Kalland
Journal	Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 41 Issue 3 Pg. 162-8 (Sep 1995) ISSN: 0340-7004 [Print] Germany
PMID	7553685 (Publication Type: Journal Article)
Chemical References	Antibodies, Monoclonal Antigens, Neoplasm Cytokines Enterotoxins HLA-DR Antigens Interferon Inducers Recombinant Fusion Proteins Superantigens enterotoxin A, Staphylococcal
Topics	Animals Antibodies, Monoclonal (therapeutic use) Antigens, Neoplasm (analysis) Colonic Neoplasms (immunology, metabolism, therapy) Cytokines (metabolism) Enterotoxins (therapeutic use) Female HLA-DR Antigens (analysis) Humans Interferon Inducers (therapeutic use) Mice Mice, SCID Recombinant Fusion Proteins (therapeutic use) Staphylococcus aureus (immunology) Superantigens (therapeutic use)

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