Cancer Immunology, Immunotherapy

, Volume 36, Issue 4, pp 215–222

Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant

Authors

  • Grant D. MacLean
    • Cross Cancer InstituteUniversity of Alberta
    • Department of MedicineUniversity of Alberta
  • Mark Reddish
    • Biomira Inc.
  • R. Rao Koganty
    • Biomira Inc.
  • Ting Wong
    • Biomira Inc.
  • Sham Gandhi
    • Biomira Inc.
  • Mark Smolenski
    • Biomira Inc.
  • John Samuel
    • Department of ImmunologyUniversity of Alberta
  • Jean Marc Nabholtz
    • Cross Cancer InstituteUniversity of Alberta
  • B. Michael Longenecker
    • Cross Cancer InstituteUniversity of Alberta
    • Department of ImmunologyUniversity of Alberta
    • Biomira Inc.
Original articles

DOI: 10.1007/BF01740902

Cite this article as:
MacLean, G.D., Reddish, M., Koganty, R.R. et al. Cancer Immunol Immunother (1993) 36: 215. doi:10.1007/BF01740902

Abstract

We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox. adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3–10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

Key words

ImmunotherapySynthetic cancer antigenGlycoconjugateSialyl-TnCancer vaccine

Copyright information

© Springer-Verlag 1993