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 language | English |
|---|---|
| Pages (from-to) | 1825-1833 |
| Number of pages | 9 |
| Journal | Annals of Oncology |
| Volume | 15 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2004 Dec 1 |
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All Science Journal Classification (ASJC) codes
- Hematology
- Oncology
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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, S. Y.; 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 journal › Article
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, S. Y.
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=19944393861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944393861&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdh472
DO - 10.1093/annonc/mdh472
M3 - Article
C2 - 15550589
AN - SCOPUS:19944393861
VL - 15
SP - 1825
EP - 1833
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 12
ER -