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Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen

British Journal of Cancer volume 85, pages 129–136 (2001)Cite this article

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Abstract

Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEAD227A bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEAD227A tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEAD227A induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10–10 M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEAD227A against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEAD227A. Thus, 5T4FabV13-SEAD227A has highly attractive properties for therapy of human NSCLC. © 2001 Cancer Research Campaign http://www.bjcancer.com

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

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Affiliations

  1. Active Biotech Research AB, Box 724, Lund, 220 07, Sweden

    G Forsberg, L Ohlsson, T Brodin, P Björk & P A Lando

  2. Paterson Institute for Cancer Research, Manchester, UK

    D Shaw & P L Stern

  3. Department of Cell and Molecular Biology, Lund University, Sweden

    M Dohlsten

Authors
  1. G Forsberg
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  2. L Ohlsson
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  3. T Brodin
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  5. P A Lando
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  6. D Shaw
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  7. P L Stern
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  8. M Dohlsten
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Forsberg, G., Ohlsson, L., Brodin, T. et al. Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen. Br J Cancer 85, 129–136 (2001). https://doi.org/10.1054/bjoc.2001.1891

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