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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Autor principal: Ballaré, C.
Otros Autores: Portela, P., Schiaffi, J., Yomha, R., Mordoh, J.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 1998
Acceso en línea:Registro en Scopus
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Registro en la Biblioteca Digital
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008 190411s1998 xx ||||fo|||| 00| 0 eng|d
024 7 |2 scopus  |a 2-s2.0-0031963756 
024 7 |2 cas  |a Antibodies, Monoclonal; Antigens, CD15; Antineoplastic Agents; Doxorubicin, 23214-92-8; Paclitaxel, 33069-62-4; sialosyl dimeric Le(x) antigen 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a BCTRD 
100 1 |a Ballaré, C. 
245 1 0 |a Reactivity of monoclonal antibody FC-2.15 against drug resistant breast cancer cells. Additive cytotoxicity of adriamycin and taxol with FC-2.15 
260 |c 1998 
270 1 0 |m Mordoh, J.; Inst. de Investigaciones Bioquimicas, 'Fundacion Campomar', Patricias Argentinas 435, 1405 Buenos Aires, Argentina; email: mordohfc@iris.iib.uba.ar 
506 |2 openaire  |e Política editorial 
504 |a Mordoh, J., Leis, S., Bravo, A.I., Podhajcer, O., Ballaré, C., Capurro, M., Kairiyama, C., Bover, L., Description of a new monoclonal antibody, FC-2.15, reactive with human breast cancer and other human neoplasias (1994) Int J Biol Markers, 9, pp. 125-134 
504 |a Capurro, M., Bover, L., Portela, P., Livingston, P., Mordoh, J., FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis x hapten Cancer Immunol Immunother, , in press 
504 |a Ballaré, C., Barrio, M., Portela, P., Mordoh, J., Functional properties of FC-2.15, a monoclonal antibody that mediates human complement cytotoxicity against breast cancer cells (1995) Cancer Immunol Immunother, 41, pp. 15-22 
504 |a Mordoh, J., Silva, C., Albarellos, M., Bravo, A.I., Kairiyama, C., Phase I clinical trial in cancer patients of a new monoclonal antibody FC-2.15 reacting with tumor proliferating cells (1995) J Immunother, 17, pp. 151-160 
504 |a McClean, S., Hill, B.T., An overview of membrane, cytosolic and nuclear proteins associated with the expression of resistance to multiple drugs in vitro (1992) Biochim Biophys Acta, 1114, pp. 107-127 
504 |a Fairchild, C., Ivy, S.P., Kao-Shan, C., Whang-Peng, J., Rosen, N., Israel, M., Melera, P., Goldsmith, M., Isolation of amplified and overexpressed DNA sequences from adriamycin-resistant human breast cancer cells (1987) Cancer Res, 47, pp. 5141-5148 
504 |a Gottesman, M.M., Pastan, I., Biochemistry of multidrug resistance mediated by the multidrug transporter (1993) Annu Rev Biochem, 62, pp. 385-427 
504 |a Salmon, S., Grogan, T., Miller, T., Scheper, R., Dalton, W., Prediction of doxorubicin resistance in vitro in myeloma, lymphoma, and breast cancer by P-glycoprotein staining (1989) J Natl Cancer Inst, 81, pp. 696-701 
504 |a Vickers, P.J., Dickson, R.B., Shoemaker, R., Cowan, K.H., A multidrug - Resistant MCF-7 human breast cancer cell line which exhibits cross-resistance to antiestrogens and hormone-independent tumor growth in vivo (1988) Mol Endocrinol, 2, pp. 886-892 
504 |a Whelan, R.D., Hill, B.T., Differential expression of steroid receptors, hsp27, and pS2 in a series of drug resistant human breast tumor cell lines derived following exposure to antitumor drugs or to fractionated X-irradiation (1993) Breast Cancer Res Treat, 26, pp. 23-39 
504 |a Soule, H.D., Vazquez, J., Long, A., Albert, S., Brennan, M., A human cell line from a pleural effusion derived from a breast carcinoma (1973) J Natl Cancer Inst, 51, pp. 1409-1415 
504 |a Bover, L., Barrio, M., Slavutsky, I., Bravo, A.I., Quintans, C., Bagnati, A., Lema, B., Mordoh, J., Description of a new human breast cancer cell line, IIB-BR-G, established from a primary undifferentiated tumor (1991) Breast Cancer Res Treat, 19, pp. 47-56 
504 |a Bravo, A.I., Sorin, I., Guman, N., Mordoh, J., Carcinoembryonic antigen and differentiation in human breast cancer (1985) J Exp Clin Cancer Res, 4, pp. 3-10 
504 |a Hakomori, S., Aberrant glycosylation in cancer cell membranes as focused on glycolipids: Overview and perspectives (1985) Cancer Res, 45, pp. 2405-2414 
504 |a Kim, Y.S., Altered glycosylation of mucin glycoproteins in colonic neoplasia (1992) J Cell Biochem (Suppl), 16 G, pp. 91-96 
504 |a Kim, Y.S., Carbohydrate antigen expression in colorectal cancer (1990) Sem Cancer Biol, 1, pp. 189-197 
504 |a Ho, S.B., Kim, Y.S., Carbohydrate antigens on cancer-associated mucin-like molecules (1991) Sem Cancer Biol, 2, pp. 389-400 
504 |a Urdal, D.L., Brentnall, T.A., Bernstein, I.D., Hakomori, S.I., A granulocyte reactive monoclonal antibody, IG10, identifies the galbl-4 (Fucal-3) GlcNAc (x determinant) expressed in HL60 cells on both glycolipid and glycoprotein molecules (1983) Blood, 62, pp. 1022-1026 
504 |a Singhal, A.K., Orntoft, T.F., Nudelman, E., Nance, S., Schibig, L., Stroud, M.R., Clausen, H., Hakomori, S., Profiles of Lewisx-containing glycoproteins and glycolipids in sera of patients with adenocarcinoma (1990) Cancer Res, 50, pp. 1375-1380 
504 |a Zhang, S., Zhang, H.S., Cordon-Cardo, C., Reuter, V.E., Singhal, A.K., Lloyd, K.O., Livingston, P.O., Selection of tumor antigens as targets for immune attack using immunohistochemistry. Blood group-related antigens Int J Cancer, , in press 
504 |a D'Arpa, P., Liu, L.F., Topoisomerase-targeting antitumor drugs (1989) Biochim Biophys Acta, 989, pp. 163-177 
504 |a Hudis, C., Seldman, A., Raptis, G., Fennelly, D., Gilewski, T., Baselga, J., Theodoulou, M., Norton, L., Sequential adjuvant therapy: The Memorial Sloan-Kettering Cancer Center experience (1996) Semin Oncol, 23, pp. 58-64 
504 |a Jordan, M.A., Toso, R.J., Thrower, D., Wilson, L., Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations (1993) Proc Natl Acad Sci USA, 90, pp. 9552-9556 
520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: This work was supported by Grants from the Fun-dación Sales (Argentina), the Fundación para la In-vestigación Prevención del Cancer (FUCA) (Argentina), and the Fundación María Calderón de la Barca (Argentina). JM is a member of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. PP is a Fellow of Funda-ción Sales. 
593 |a Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 
593 |a Inst. Invest. Bioquimicas Fund. C., Buenos Aires, Argentina 
593 |a Hospital Rivadavia, Buenos Aires, Argentina 
593 |a Inst. Invest. Bioquimicas Fund. C., Patricias Argentinas 435, 1405 Buenes Aires, Argentina 
690 1 0 |a ADRIAMYCIN 
690 1 0 |a BREAST CANCER 
690 1 0 |a MDR 
690 1 0 |a MONOCLONAL ANTIBODY 
690 1 0 |a TAXOL 
690 1 0 |a ANTIBODY 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a COMPLEMENT 
690 1 0 |a CYCLOPHOSPHAMIDE 
690 1 0 |a DOXORUBICIN 
690 1 0 |a EPIRUBICIN 
690 1 0 |a FLUOROURACIL 
690 1 0 |a MEMBRANE ANTIGEN 
690 1 0 |a MONOCLONAL ANTIBODY 
690 1 0 |a PACLITAXEL 
690 1 0 |a TUMOR ANTIGEN 
690 1 0 |a ANTIGEN EXPRESSION 
690 1 0 |a ANTINEOPLASTIC ACTIVITY 
690 1 0 |a ARTICLE 
690 1 0 |a BLOOD GROUP LEWIS SYSTEM 
690 1 0 |a BREAST CANCER 
690 1 0 |a CANCER CELL 
690 1 0 |a CANCER CELL CULTURE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a CYTOLYSIS 
690 1 0 |a CYTOTOXICITY 
690 1 0 |a FEMALE 
690 1 0 |a FLOW CYTOMETRY 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a MOLECULAR RECOGNITION 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a ANTIBODIES, MONOCLONAL 
690 1 0 |a ANTIGENS, CD15 
690 1 0 |a ANTINEOPLASTIC AGENTS 
690 1 0 |a BREAST NEOPLASMS 
690 1 0 |a CELL SURVIVAL 
690 1 0 |a DOXORUBICIN 
690 1 0 |a DRUG RESISTANCE, NEOPLASM 
690 1 0 |a FEMALE 
690 1 0 |a HUMANS 
690 1 0 |a PACLITAXEL 
690 1 0 |a TUMOR CELLS, CULTURED 
700 1 |a Portela, P. 
700 1 |a Schiaffi, J. 
700 1 |a Yomha, R. 
700 1 |a Mordoh, J. 
773 0 |d 1998  |g v. 47  |h pp. 163-170  |k n. 2  |p Breast Cancer Res. Treat.  |x 01676806  |t Breast Cancer Research and Treatment 
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