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Specificity of the IgG Response in Mice and Human Breast Cancer Patients Following Immunization Against Synthetic Sialyl-Tn, An Epitope with Possible Functional Significance in Metastasis

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Book cover Antigen and Antibody Molecular Engineering in Breast Cancer Diagnosis and Treatment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 353))

Abstract

Several investigators have shown that the expression of the sialyl-Tn (STn) epitope on cancer associated mucins is associated with a poor prognosis in several human cancers suggesting that STn may have functional significance in metastasis. We postulate that antibodies against the STn-epitope can inhibit metastasis. We generated a synthetic “mimic”, NANAα(2-6)GalNAcα-O-Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANAα(2-6)GalNAcα-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm and a “vaccine” containing STn-KLH plus Detox™ adjuvant was formulated. The immunogenicity of the vaccine was evaluated in BALB/c mice and in metastatic breast cancer patients. The specificity and titres of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid phases. OSM is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 μg of STn-KLH produced a median IgG titre of over 1: 5000 on solid phase OSM. Anti-OSM IgG monoclonal antibodies generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens.

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Authors and Affiliations

  1. Immunotherapeutics Division, Biomira Inc., 2011 - 94 Street, Edmonton, Alberta, T6N 1H1, Canada

    B. Michael Longenecker, Mark Reddish & Rao Koganty

  2. Department of Immunology, University of Alberta, Edmonton, Alberta, T6N 2H7, Canada

    B. Michael Longenecker

  3. Department of Medicine, University of Alberta, Edmonton, Alberta, T6N 2R7, Canada

    Grant D. MacLean

  4. Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada

    B. Michael Longenecker & Grant D. MacLean

Authors
  1. B. Michael Longenecker
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  2. Mark Reddish
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  3. Rao Koganty
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  4. Grant D. MacLean
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Editors and Affiliations

  1. Cancer Research Fund of Contra Costa, Walnut Creek, California, USA

    Roberto L. Ceriani

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© 1994 Springer Science+Business Media New York

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Longenecker, B.M., Reddish, M., Koganty, R., MacLean, G.D. (1994). Specificity of the IgG Response in Mice and Human Breast Cancer Patients Following Immunization Against Synthetic Sialyl-Tn, An Epitope with Possible Functional Significance in Metastasis. In: Ceriani, R.L. (eds) Antigen and Antibody Molecular Engineering in Breast Cancer Diagnosis and Treatment. Advances in Experimental Medicine and Biology, vol 353. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2443-4_11

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  • DOI: https://doi.org/10.1007/978-1-4615-2443-4_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6038-4

  • Online ISBN: 978-1-4615-2443-4

  • eBook Packages: Springer Book Archive

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