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Titolo:
Monoclonal antibody therapy with Edrecolomab in breast cancer patients: Monitoring of elimination of disseminated cytokeratin-positive tumor cells inbone marrow
Autore:
Braun, S; Hepp, F; Kentenich, CRM; Janni, W; Pantel, K; Riethmuller, G; Willgeroth, F; Sommer, HL;
Indirizzi:
Univ Munich, Inst Immunol, D-80337 Munich, Germany Univ Munich Munich Germany D-80337 Inst Immunol, D-80337 Munich, Germany Univ Munich, Klinikum Innenstadt, Frauenklin 1, D-80337 Munich, Germany Univ Munich Munich Germany D-80337 Frauenklin 1, D-80337 Munich, Germany Univ Hamburg, Klinikum Eppendorf, Frauenklin, D-20251 Hamburg, Germany Univ Hamburg Hamburg Germany D-20251 rauenklin, D-20251 Hamburg, Germany
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 12, volume: 5, anno: 1999,
pagine: 3999 - 4004
SICI:
1078-0432(199912)5:12<3999:MATWEI>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPITHELIAL MEMBRANE ANTIGEN; RANDOMIZED TRIAL; MICROMETASTASES; EXPRESSION; MOLECULES; CARCINOMA; TARGET;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Braun, S Univ Munich, Inst Immunol, Maistr 11, D-80337 Munich, Germany Univ Munich Maistr 11 Munich Germany D-80337 337 Munich, Germany
Citazione:
S. Braun et al., "Monoclonal antibody therapy with Edrecolomab in breast cancer patients: Monitoring of elimination of disseminated cytokeratin-positive tumor cells inbone marrow", CLIN CANC R, 5(12), 1999, pp. 3999-4004

Abstract

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 breastcancer 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 = 0.003,6 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 marrow and typed EpCAM expression, This allowed us to monitor the cytotoxicelimination 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.

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Documento generato il 25/11/20 alle ore 18:44:08