TY - JOUR
T1 - FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis(x) hapten
AU - Capurro, Mariana
AU - Bover, Laura
AU - Portela, Paula
AU - Livingston, Philip
AU - Mordoh, José
N1 - Funding Information:
AcknowledgementsmThis work has been supported by grants from the Fundación Sales (Argentina), the Fundación para la Investigación y Prevención del Cáncer (FUCA), Argentina, the Fundación Pedro F. Mosoteguy (Argentina) and the National Institutes of Health (USA), grant 61422. J.M. and L.B. belong to the Career Investigator of the Consejo Nacional de Investigaciones Cient́õficas y Técnicas (CON-ICET, Argentina), and M.C. is a Fellow of the latter institution. Helpful suggestions and assistance by Dr. Kenneth Lloyd, Memorial Sloan-Kettering Cancer Center, were appreciated. We are grateful to A. Robinson, M.D., Hematology Department, Hospital Naval Pedro Mallo, Argentina, and to A. Kohan, M.D., Hematology Department, Hospital de Cĺõnicas, Argentina, for the provision of blood from normal volunteers and CML patients respectively. We would like to thank Dr. Cecilia Carbone, Faculty of Veterinary Sciences, University of La Plata, Buenos Aires, Argentina, for the provision of mice.
PY - 1998
Y1 - 1998
N2 - FC-2.15 is a murine IgM monoclonal antibody that recognizes breast and colon human carcinomas, chronic myeloid leukemias, Steinberg cells of Hodgkin's lymphoma and some normal cells, such as peripheral polymorphonuclear granulocytes. It has been previously demonstrated that FC- 2.15 recognizes the carbohydrate moiety of different glycoproteins. FC-2.15 is able to mediate the in vitro lysis of Ag-2.15+ cells by human complement. In a phase I clinical trial, FC-2.15 induced antitumor responses and reversible neutropenia was its main toxicity. In this work, analysis of epitope specificity has demonstrated that FC-2.15 specifically recognizes terminally exposed Lewis(x) trisaccharide but not sialyl-Lewis(x), Lewis(a), trifucosylated Lewis(y), blood-group antigens A and B, globo H and gangliosides. In polymorphonuclear granulocytes (PMN), myeloid leukemic cells and colon carcinoma T84 cells, Lewis(x) was found to be almost exclusively N- linked to the protein core, whereas in breast carcinoma MCF-7 cells, Lewis(x) appeared to be mostly O-linked. Treatment with neuraminidase increased detection by FC-2.15 in normal PMN, myeloid leukemia cells and T84 cells but not in MCF-7 cells.
AB - FC-2.15 is a murine IgM monoclonal antibody that recognizes breast and colon human carcinomas, chronic myeloid leukemias, Steinberg cells of Hodgkin's lymphoma and some normal cells, such as peripheral polymorphonuclear granulocytes. It has been previously demonstrated that FC- 2.15 recognizes the carbohydrate moiety of different glycoproteins. FC-2.15 is able to mediate the in vitro lysis of Ag-2.15+ cells by human complement. In a phase I clinical trial, FC-2.15 induced antitumor responses and reversible neutropenia was its main toxicity. In this work, analysis of epitope specificity has demonstrated that FC-2.15 specifically recognizes terminally exposed Lewis(x) trisaccharide but not sialyl-Lewis(x), Lewis(a), trifucosylated Lewis(y), blood-group antigens A and B, globo H and gangliosides. In polymorphonuclear granulocytes (PMN), myeloid leukemic cells and colon carcinoma T84 cells, Lewis(x) was found to be almost exclusively N- linked to the protein core, whereas in breast carcinoma MCF-7 cells, Lewis(x) appeared to be mostly O-linked. Treatment with neuraminidase increased detection by FC-2.15 in normal PMN, myeloid leukemia cells and T84 cells but not in MCF-7 cells.
KW - Carcinoma
KW - FC-2.15
KW - Lewis(x)
KW - Monoclonal antibody
KW - Neutrophils
UR - http://www.scopus.com/inward/record.url?scp=0031934951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031934951&partnerID=8YFLogxK
U2 - 10.1007/s002620050451
DO - 10.1007/s002620050451
M3 - Article
C2 - 9490204
AN - SCOPUS:0031934951
SN - 0340-7004
VL - 45
SP - 334
EP - 339
JO - Cancer Immunology Immunotherapy
JF - Cancer Immunology Immunotherapy
IS - 6
ER -