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

Background: BrevaRex(R) mAb-AR20.5 is a murine anti-MUCI monoclonal antibody generated to induce MUCI antigen- specific immune responses through the formation of immune complexes with circulating MUCI and/or MUCI-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 MUCI-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-MUCI antibodies. Immune responses were most prominent in the 2-mg dose cohort for all parameters tested, and treatment-emergent MUCI-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 MUCI induces MUCI-specific immune responses in advanced cancer patients. Anti-MUCI 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.