Monoclonal antibody therapy with edrecolomab in breast cancer patients: monitoring of elimination of disseminated cytokeratin-positive tumor cells in bone marrow.
Despite current advances in antibody-based immunotherapy of breast and colorectal cancer, we have recently shown that the actual target cells (e.g., tumor cells disseminated to bone marrow) may express a heterogeneous pattern of the potential target antigens. Tumor antigen heterogeneity may therefore represent an important limitation of the efficacy of monospecific antibody therapy. To measure the efficacy of such a monospecific approach, we analyzed the elimination of tumor cells coexpressing the epithelial cell adhesion molecule (EpCAM) under therapy with murine monoclonal antibody 17-1A (Edrecolomab) directed against EpCAM. In bone marrow aspirates from 10 breast cancer patients with metastatic (n = 8) and locoregional recurrence (n = 2), tumor cells were identified with the antibody A45-B/B3 directed against the epithelial differentiation marker cytokeratin (CK) and simultaneously typed for EpCAM expression using the antibody 17-1A. Patients were treated with a single dose of 500 mg of Edrecolomab and monitored by bone marrow analyses before and at days 5-7 after antibody treatment. In all 10 patients, we assessed a marked reduction in the mean numbers of both CK+ cells (73 versus 15; P = 0.003, t test) and EpCAM+/CK+ cells (17 versus 1; P = 0.003, t test) per 10(6) bone marrow cells. Complete elimination of EpCAM+ cells was possible in four patients. We conclude that Edrecolomab can be used in breast cancer patients to target isolated EpCAM+/CK+ cancer cells. Using CK-based immunoassays, we reliably detected residual tumor cells in bone marrow and typed EpCAM expression. This allowed us to monitor the cytotoxic elimination of such cells after Edrecolomab application. Selection of EpCAM-/ CK+ tumor clones showed that further antibodies directed against tumor-associated antigens are warranted to improve the efficacy of monospecific approaches.
Braun
S
S
I. Frauenklinik, Klinikum Innenstsdt, Ludwig-Maximilians-Universität, Munich, Germany. sbraun@fk-i.med.uni-muenchen.de
Hepp
F
F
Kentenich
C R
CR
Janni
W
W
Pantel
K
K
Riethmüller
G
G
Willgeroth
F
F
Sommer
H L
HL
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000276:immunology; D001854:Bone Marrow Cells / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis* / Q000276:immunology; D010865:Pilot Projects; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D006131:Growth Inhibitors; C400149:Edrecolomab; D007633:Keratins