Human-human hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients.

Lymphocytes from lymph nodes obtained from breast cancer patients undergoing mastectomy were fused with the 0467.3, UC729HF2, or KR-12 human cell lines, totaling 42 fusions with lymphocytes from 23 patients. A total of 1696 human-human hybridomas were generated, 675 (39.8%) of which produced human IgG and/or IgM. Seventy-three human hybridomas produced antibodies binding to autologous malignant breast tissue and/or MCF-7 cells, as assayed by immunohistology or by cell-binding enzyme-linked immunosorbent assay. Twelve of these hybridomas, all reacting with malignant breast tissue, were subcloned to stabilize the production of human immunoglobulin. The reaction patterns of these 12 human monoclonal antibodies were investigated further by immunohistology on formalin-fixed, paraffin-embedded tissues. The reaction patterns of the various antibodies showed substantial variation and the antibodies reacted with a varying frequency with antigens expressed by different malignant breast tumors. One of these antibodies, MAC 40/43 (IgM), reacted with malignant breast and colon carcinomas and other epithelial derived neoplasms but did not react with normal breast tissue or with other normal and malignant tissues tested, except for a weak reaction with certain normal epithelial tissues. The antigen defined by MAC 40/43 was identified as a Mr approximately equal to 47,000 glycoprotein.

[1]  D. Edwards,et al.  Cancer 43 , 000 Membrane Glycoprotein Associated with Human Breast r M Monoclonal Antibody Identification and Characterization of a Updated Version , 2006 .

[2]  S. Hakomori,et al.  Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. , 1985, Cancer research.

[3]  Robert A. Bloodgood,et al.  Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation. , 1985, Journal of immunological methods.

[4]  J. Roder,et al.  A human hybrid myeloma for production of human monoclonal antibodies. , 1984, Journal of immunology.

[5]  G. Springer.  T and Tn, general carcinoma autoantigens. , 1984, Science.

[6]  I. Royston,et al.  UC 729-6, a human lymphoblastoid B-cell line useful for generating antibody-secreting human-human hybridomas. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Foon,et al.  Determination of the optimal human cell lines for development of human hybridomas. , 1983, Journal of immunology.

[8]  R. Ceriani,et al.  Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule , 1983, Somatic cell genetics.

[9]  R. Cote,et al.  Generation of human monoclonal antibodies reactive with cellular antigens. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Roder,et al.  The production of monoclonal antibodies from human lymphocytes. , 1983, Immunology today.

[11]  H. Kunkel,et al.  Use of Epstein-Barr virus-transformed B cell lines for the generation of immunoglobulin-producing human B cell hybridomas , 1982, The Journal of experimental medicine.

[12]  R. Saxton,et al.  Human antibody to OFA-I, a tumor antigen, produced in vitro by Epstein-Barr virus-transformed human B-lymphoid cell lines. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Schlom,et al.  Generation of human monoclonal antibodies reactive with human mammary carcinoma cells. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Margulies,et al.  A simple method for polyethylene glycol-promoted hybridization of mouse myeloma cells , 1977, Somatic cell genetics.

[15]  C. Milstein,et al.  Continuous cultures of fused cells secreting antibody of predefined specificity , 1975, Nature.

[16]  C. Taylor,et al.  Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells. , 1985, Cancer research.

[17]  J. Douillard,et al.  Enzyme-linked immunosorbent assay for screening monoclonal antibody production using enzyme-labeled second antibody. , 1983, Methods in enzymology.

[18]  G. Dreesman,et al.  Utilization of the biotin/avidin system to amplify the sensitivity of the enzyme-linked immunosorbent assay (ELISA). , 1983, Journal of immunological methods.