Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15

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 re...

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Autores principales:	Ballaré, Cecilia J., Portela, Paula
Publicado:	1998
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v47_n2_p163_Ballare http://hdl.handle.net/20.500.12110/paper_01676806_v47_n2_p163_Ballare
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_01676806_v47_n2_p163_Ballare
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spelling	paper:paper_01676806_v47_n2_p163_Ballare2023-06-08T15:16:43Z Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15 Ballaré, Cecilia J. Portela, Paula 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 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. Fil:Ballaré, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Portela, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v47_n2_p163_Ballare http://hdl.handle.net/20.500.12110/paper_01676806_v47_n2_p163_Ballare
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Ballaré, Cecilia J. Portela, Paula Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
topic_facet	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
description	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.
author	Ballaré, Cecilia J. Portela, Paula
author_facet	Ballaré, Cecilia J. Portela, Paula
author_sort	Ballaré, Cecilia J.
title	Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
title_short	Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
title_full	Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
title_fullStr	Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
title_full_unstemmed	Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15
title_sort	reactivity of monoclonal antibody fc-2.15 against drug resistant breast cancer cells. additive cytotoxicity of adriamycin and taxol with fc-2.15
publishDate	1998
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v47_n2_p163_Ballare http://hdl.handle.net/20.500.12110/paper_01676806_v47_n2_p163_Ballare
work_keys_str_mv	AT ballarececiliaj reactivityofmonoclonalantibodyfc215againstdrugresistantbreastcancercellsadditivecytotoxicityofadriamycinandtaxolwithfc215 AT portelapaula reactivityofmonoclonalantibodyfc215againstdrugresistantbreastcancercellsadditivecytotoxicityofadriamycinandtaxolwithfc215
_version_	1768545876009025536

Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15

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