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Annals of Oncology 2004 15(12):1825-1833; doi:10.1093/annonc/mdh472
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© 2004 European Society for Medical Oncology

Original Article

Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity

J. S. de Bono1,*, S. Y. Rha1, J. Stephenson1,2, B. C. Schultes3, P. Monroe1, G. S. Eckhardt1, L. A. Hammond1, T. L. Whiteside4, C. F. Nicodemus5, J. M. Cermak5, E. K. Rowinsky1 and A. W. Tolcher1

1 Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX; 2 Brooke Army Medical Center, Fort Sam, Houston, TX; 3 AltaRex, Waltham, MA; 4 University of Pittsburgh Cancer Institute, Pittsburgh, PA; 5 Unither Pharmaceuticals, Wellesley, MA, USA

* Correspondence to: Dr J. S. de Bono, Centre for Cancer Therapeutics, Institute for Cancer Research, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel: +44-20-8722-4302; Fax: +44-20-8642-7979; Email: jdebono{at}icr.ac.uk

Background: BrevaRex® mAb-AR20.5 is a murine anti-MUC1 monoclonal antibody generated to induce MUC1 antigen-specific immune responses through the formation of immune complexes with circulating MUC1 and/or MUC1-expressing tumor cells that may target these immune complexes (IC) to receptors on dendritic cells (DCs).

Patients and methods: A phase I study focusing on safety and immunology evaluated 1, 2 and 4-mg doses. Seventeen patients with MUC1-positive cancers received intravenous infusions of the antibody over 30 min on weeks 1, 3, 5, 9, 13 and 17 of treatment.

Results: mAb-AR20.5 was well-tolerated, not associated with dose-limiting toxicity, and did not induce hypersensitivity reactions. Overall, five of 15 evaluable patients developed human anti-mouse antibodies (HAMA), five developed anti-idiotypic antibodies (Ab2) and seven developed anti-MUC1 antibodies. Immune responses were most prominent in the 2-mg dose cohort for all parameters tested, and treatment-emergent MUC1-specific T-cell responses were detected in five of 10 evaluable patients treated with mAb-AR20.5.

Conclusions: The injection of a murine antibody to MUC1 induces MUC1-specific immune responses in advanced cancer patients. Anti-MUC1 antibody increases correlated with decrease or stabilization of CA15.3 levels (P=0.03). The 2-mg dose of mAb-AR20.5 showed strongest biological activity, and will be evaluated in future efficacy trials.

Key words: antibody, BrevaRex®, mAb-AR20.5, MUC1, phase I trial


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