title: Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity.
abstract: 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).
  
  
  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.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. jdebono@icr.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
authors.forename: S Y
authors.initials: SY
authors.lastname: Rha
authors.forename: J
authors.initials: J
authors.lastname: Stephenson
authors.forename: B C
authors.initials: BC
authors.lastname: Schultes
authors.forename: P
authors.initials: P
authors.lastname: Monroe
authors.forename: G S
authors.initials: GS
authors.lastname: Eckhardt
authors.forename: L A
authors.initials: LA
authors.lastname: Hammond
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: C F
authors.initials: CF
authors.lastname: Nicodemus
authors.forename: J M
authors.initials: JM
authors.lastname: Cermak
authors.forename: E K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: A W
authors.initials: AW
authors.lastname: Tolcher
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000917:Antibody Formation / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D018396:Mucin-1; C499880:mAb-AR20.5