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Abstract:

Monoclonal antibody (MAb) FC-2.15 recognizes Lewis x antigen (Le(x)-Ag) expressed on the cell surface of most human breast cancer cells. FC-2.15 displays important human complement (C')-mediated cytotoxicity (CMC) against its target cells. In this study the reactivity of FC-2.15 against drug resistant-breast cancer cells was investigated, as well as the possibility to combine the antitumor activities of this MAb with adriamycin (Adr) or taxol. Since resistant clones with altered expression of tumor-associated antigens usually emerge after chemotherapy, the expression of Le(x)-Ag was analyzed in Adr(R) MCF-7 breast cancer cells (Adr resistant subline) and in tumor samples from nine patients with locally advanced breast carcinoma who were treated with FEC chemotherapy. A flow cytometry assay showed that most of Adr(R) MCF-7 cells, as well as wild type (WT) cells, expressed Le(x)-Ag; however, the Le(x) epitope is probably bound to different backbones in these cells. When the cytotoxic ability of FC-2.15 against WT and Adr(R) MCF-7 cells was compared, it was found that a 90 min treatment with FC-2.15 plus C' induced similar CMC against both cell lines. An important cytolysis was obtained at 5 μg/ml FC-2.15, reaching a plateau at 25 μg/ml, at which cell population was diminished to 21.1% for WT and 27.9 for Adr(R) MCF-7 cells. Regarding human tumors, Le(x)-Ag expression was evaluated in samples obtained before and in most cases after chemotherapy, and it could be observed that: 1) before treatment, tumor samples from all patients analyzed (responders and non-responders to chemotherapy) were FC-2.15-positive; 2) the presence of Le(x)-Ag was not modified after treatment. The combined action of Adr or taxol with FC-2.15 was then evaluated. WT and Adr(R) MCF-7 cells were cultured with Adr or taxol followed by an incubation with different FC-2.15 concentrations plus C'. When the effect of Adr alone was determined, ID50 were 1 x 10-7 M for WT and 4.2 x 10-5 M for Adr(R) MCF-7 cells. The cytotoxic ability of taxol alone was also tested, and ID50 were 6.4 x 10-9 M for WT and 3.1 x 10-6 M for Adr(R) MCF-7 cells. When FC-2.15 was added to Adr or taxol, the cytotoxicity of the drug-FC-2.15 combined treatment was always higher than the isolated effects, showing additive cytotoxicity at the different concentrations tested and with both cell lines. Our results suggest that FC-2.15 may be a useful agent against breast tumor cells which survive chemotherapy with Adr or taxol.

Registro:

Documento: Artículo
Título:Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
Autor:Ballaré, C.; Portela, P.; Schiaffi, J.; Yomha, R.; Mordoh, J.
Filiación:Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Inst. Invest. Bioquimicas Fund. C., Buenos Aires, Argentina
Hospital Rivadavia, Buenos Aires, Argentina
Inst. Invest. Bioquimicas Fund. C., Patricias Argentinas 435, 1405 Buenes Aires, Argentina
Palabras clave:Adriamycin; Breast cancer; MDR; Monoclonal antibody; Taxol; antibody; antineoplastic agent; complement; cyclophosphamide; doxorubicin; epirubicin; fluorouracil; membrane antigen; monoclonal antibody; paclitaxel; tumor antigen; antigen expression; antineoplastic activity; article; blood group Lewis system; breast cancer; cancer cell; cancer cell culture; controlled study; cytolysis; cytotoxicity; female; flow cytometry; human; human cell; molecular recognition; priority journal; Antibodies, Monoclonal; Antigens, CD15; Antineoplastic Agents; Breast Neoplasms; Cell Survival; Doxorubicin; Drug Resistance, Neoplasm; Female; Humans; Paclitaxel; Tumor Cells, Cultured
Año:1998
Volumen:47
Número:2
Página de inicio:163
Página de fin:170
DOI: http://dx.doi.org/10.1023/A:1005949118919
Título revista:Breast Cancer Research and Treatment
Título revista abreviado:Breast Cancer Res. Treat.
ISSN:01676806
CODEN:BCTRD
CAS:Antibodies, Monoclonal; Antigens, CD15; Antineoplastic Agents; Doxorubicin, 23214-92-8; Paclitaxel, 33069-62-4; sialosyl dimeric Le(x) antigen
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v47_n2_p163_Ballare

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Citas:

---------- APA ----------
Ballaré, C., Portela, P., Schiaffi, J., Yomha, R. & Mordoh, J. (1998) . Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15. Breast Cancer Research and Treatment, 47(2), 163-170.
http://dx.doi.org/10.1023/A:1005949118919
---------- CHICAGO ----------
Ballaré, C., Portela, P., Schiaffi, J., Yomha, R., Mordoh, J. "Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15" . Breast Cancer Research and Treatment 47, no. 2 (1998) : 163-170.
http://dx.doi.org/10.1023/A:1005949118919
---------- MLA ----------
Ballaré, C., Portela, P., Schiaffi, J., Yomha, R., Mordoh, J. "Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15" . Breast Cancer Research and Treatment, vol. 47, no. 2, 1998, pp. 163-170.
http://dx.doi.org/10.1023/A:1005949118919
---------- VANCOUVER ----------
Ballaré, C., Portela, P., Schiaffi, J., Yomha, R., Mordoh, J. Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15. Breast Cancer Res. Treat. 1998;47(2):163-170.
http://dx.doi.org/10.1023/A:1005949118919