Isolation and characterization of a human monoclonal antibody which reacts with breast and colorectal carcinoma.
A human monoclonal antibody with specificity for breast and colorectal carcinoma has been isolated after hybridoma formation between regional lymph node lymphocytes from a patient with breast carcinoma and a mouse x human heteromyeloma (SPAZ-4). The monoclonal, MAB 15.2.3, is an IgM, kappa, which binds to an epitope found on at least four glycoproteins with approximate molecular weights of 37, 39, 43 and 56 kilodaltons (kD). These antigens are expressed intracellularly and on the surface of breast and colorectal carcinoma cells and their level of expression is increased by treatment with recombinant human leukocyte (IFN-alpha A) or immune (IFN-gamma) interferon. Analysis of formalin-fixed tumor cell lines indicates specificity for carcinomas. Similarly, immunostaining of paraffin-embedded tissue indicates both cell membrane and intracytoplasmic reactivity with breast (8 of 12), colorectal (3 of 4) and prostate (1 of 3) carcinomas. By employing a series of enzymes which specifically cleave sugar residues on proteins, it was demonstrated that the binding of MAB 15.2.3 could be increased. These observations suggest that the epitope recognized by MAB 15.2.3. is protein in nature and expressed on a series of glycoproteins. Pretreatment of Colo 205 (human colorectal carcinoma) cells with MAB 15.2.3 prior to implantation into nude mice, results in a reduction in the size and weight of tumors. With appropriate genetic engineering, resulting in the conversion of this antibody to an IgG, MAB 15.2.3. could prove of value for the diagnosis and ultimately the therapy of human breast and colorectal carcinomas.
Goldstein
N I
NI
ImClone Systems, Inc., New York, New York 10014.
Nagle
R
R
Villar
H
H
Hersh
E
E
Fisher
P B
PB
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D011994:Recombinant Proteins; D012004:Rectal Neoplasms / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma