A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer

Br J Cancer. 1996 Oct;74(8):1292-6. doi: 10.1038/bjc.1996.532.


Studies in animal models of mouse mammary carcinoma have shown that ovine submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective in stimulating an immune response and inhibiting tumour growth. In similar studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide has been shown to be important in modulating the immune response to antigen possibly by inhibiting suppresser T-cell activity. In a clinical trial assessing the efficacy and toxicity of synthetic STn, patients with metastatic breast cancer were randomised to receive 100 micrograms STn linked to keyhole limpet haemocyanin (KLH) with DETOX-B adjuvant given by subcutaneous injection at weeks 0, 2, 5 and 9 with or without low-dose cyclophosphamide (CTX, 300 mg m-2) pretreatment, 3 days before the start of immunotherapy. Patients with responding or stable disease after the first four injections were eligible to receive STn-KLH at 4 week intervals. The main toxicity noted was the development of subcutaneous granulomata at injection sites. Of 23 patients randomised, 18 received four injections, 5 patients having developed progressive disease during the initial 12 week period. Two minor responses were noted in the 18 patients who received four active specific immunotherapy (ASI) injections and a further five patients had stable disease. Six patients continued ASI at 4 week intervals and a partial response was noted in a patient who had previously had stable disease. All patients developed IgG and IgM responses to sialyl-Tn and levels of IgM antibodies were significantly higher in those patients who were pretreated with CTX. Measurable tumour responses have been recorded following ASI with STn-KLH plus DETOX and the immunomodulatory properties of low-dose CTX have been confirmed.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Antibodies, Neoplasm / biosynthesis
  • Antibodies, Neoplasm / blood
  • Antigens, Tumor-Associated, Carbohydrate / therapeutic use*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cyclophosphamide / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Hemocyanins / therapeutic use*
  • Humans
  • Immunoconjugates / therapeutic use*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / blood
  • Immunotherapy, Active*
  • Middle Aged
  • Sensitivity and Specificity


  • Adjuvants, Immunologic
  • Antibodies, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • Immunoconjugates
  • Immunoglobulin G
  • Immunoglobulin M
  • sialosyl-Tn antigen
  • Cyclophosphamide
  • Hemocyanins
  • keyhole-limpet hemocyanin