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 Bono, SunYoung Rha, J. Stephenson, B. C. Schultes, P. Monroe, G. S. Eckhardt, L. A. Hammond, T. L. Whiteside, C. F. Nicodemus, J. M. Cermak, E. K. Rowinsky, A. W. Tolcher

Research output: Contribution to journalArticle

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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). 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.

Original languageEnglish
Pages (from-to)1825-1833
Number of pages9
JournalAnnals of Oncology
Volume15
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1

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Cellular Immunity
Anti-Idiotypic Antibodies
Antibodies
Neoplasms
Antigen-Antibody Complex
Intravenous Immunoglobulins
Histocompatibility Antigens Class II
Allergy and Immunology
Intravenous Infusions
Dendritic Cells
Hypersensitivity
Monoclonal Antibodies
mAb-AR20.5
T-Lymphocytes
Safety
Injections
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

de Bono, J. S. ; Rha, SunYoung ; Stephenson, J. ; Schultes, B. C. ; Monroe, P. ; Eckhardt, G. S. ; Hammond, L. A. ; Whiteside, T. L. ; Nicodemus, C. F. ; Cermak, J. M. ; Rowinsky, E. K. ; Tolcher, A. W. / Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer : Evidence for the activation of humoral and cellular antitumor immunity. In: Annals of Oncology. 2004 ; Vol. 15, No. 12. pp. 1825-1833.
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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{\circledR} 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.",
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de Bono, JS, Rha, S, Stephenson, J, Schultes, BC, Monroe, P, Eckhardt, GS, Hammond, LA, Whiteside, TL, Nicodemus, CF, Cermak, JM, Rowinsky, EK & Tolcher, AW 2004, 'Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: Evidence for the activation of humoral and cellular antitumor immunity', Annals of Oncology, vol. 15, no. 12, pp. 1825-1833. https://doi.org/10.1093/annonc/mdh472

Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer : Evidence for the activation of humoral and cellular antitumor immunity. / de Bono, J. S.; Rha, SunYoung; Stephenson, J.; Schultes, B. C.; Monroe, P.; Eckhardt, G. S.; Hammond, L. A.; Whiteside, T. L.; Nicodemus, C. F.; Cermak, J. M.; Rowinsky, E. K.; Tolcher, A. W.

In: Annals of Oncology, Vol. 15, No. 12, 01.12.2004, p. 1825-1833.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer

T2 - Evidence for the activation of humoral and cellular antitumor immunity

AU - de Bono, J. S.

AU - Rha, SunYoung

AU - Stephenson, J.

AU - Schultes, B. C.

AU - Monroe, P.

AU - Eckhardt, G. S.

AU - Hammond, L. A.

AU - Whiteside, T. L.

AU - Nicodemus, C. F.

AU - Cermak, J. M.

AU - Rowinsky, E. K.

AU - Tolcher, A. W.

PY - 2004/12/1

Y1 - 2004/12/1

N2 - 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.

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