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

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 cyclo...

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Bibliographic Details
Published in:British journal of cancer 1996-10, Vol.74 (8), p.1292-1296
Main Authors: MILES, D. W, TOWLSON, K. E, GRAHAM, R, REDDISH, M, LONGENECKER, B. M, TAYLOR-PAPADIMITRIOU, J, RUBENS, R. D
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Adult
Aged
Antibodies, Neoplasm - biosynthesis
Antibodies, Neoplasm - blood
Antigens, Tumor-Associated, Carbohydrate - therapeutic use
Antineoplastic agents
Biological and medical sciences
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - therapy
Chemotherapy, Adjuvant
Combined Modality Therapy
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
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
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Sensitivity and Specificity
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1996.532