Monoclonal antibody therapy with Edrecolomab in breast cancer patients: Monitoring of elimination of disseminated cytokeratin-positive tumor cells inbone marrow

Despite current advances in antibody-based immunotherapy of breast and colo rectal cancer, we have recently shown that the actual target cells (e.g., t umor cells disseminated to bone marrow) may express a heterogeneous pattern of the potential target antigens, Tumor antigen heterogeneity may therefor e represent an important limitation of the efficacy of monospecific antibod y therapy. To measure the efficacy of such a monospecific approach, we anal yzed the elimination of tumor cells coexpressing the epithelial cell adhesi on molecule (EpCAM) under therapy with murine monoclonal antibody 17-1A (Ed recolomab) 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 t he epithelial differentiation marker cytokeratin (CK) and simultaneously ty ped for EpCAM expression using the antibody 17-1A, Patients were treated wi th a single dose of 500 mg of Edrecolomab and monitored by bone marrow anal yses before and at days 5-7 after antibody treatment. In all 10 patients, w e assessed a marked reduction in the mean numbers of both CK+ cells (73 ver sus 15; P = 0.003, t test) and EpCAM(+)/CK+ cells (17 versus 1; P = 0.003, 6 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 m arrow 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 a pproaches.