Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes an immunoglobulin G1 mouse monoclonal antibody (MCA) 44-3A6 directed against a human adenocarcinoma of the lung, cell line A549. This hybrid is a fusion product of the mouse myeloma SP 2/0.Ag14 and spleen cells from a BALB/c mouse which had been hyperimmunized with A549. Live cell radioimmunoassays, immunofluorescences, and fluorescent activated cell sorter analysis indicate that MCA 44-3A6 reacts with a cell surface antigen. Western blot analysis identifies a major antigen band with the apparent molecular weight of 40,000. Enzyme treatment of A549 target plates shows that the antigen is sensitive to proteases. This MCA does not react with carcinoembryonic antigen. Patients having a variety of different lung carcinomas do not appear to have detectable antigen in their serum, nor does the antigen appear to be shed into culture supernatants by human lung carcinoma cell lines. The antigen is preserved in formalin-fixed, paraffin-embedded tissue sections and shows a cell surface and/or cytoplasmic staining pattern. Immunohistochemical staining of various bronchopulmonary carcinomas demonstrated binding to be restricted to tumors with features of "glandular" differentiation. This MCA may have clinical and diagnostic utility due to its selective binding for a subset of carcinomas of the lung.
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PMID:Monoclonal antibody 44-3A6 as a probe for a novel antigen found on human lung carcinomas with glandular differentiation. 241 99

Sixteen tumor markers are reviewed, and measured to the ideal: produced by the tumor cell alone absent in health and in benign disease present in all patients with a given malignancy level in the blood representative of tumor mass detectable in occult disease. The only marker that approaches the ideal is human chorionic gonadotropin (HCG) in gestational trophoblastic tumors. In this malignancy, the HCG level suggests the diagnosis and stage, confirms response to therapy, and predicts relapse. The three most widely used and intensely studied tumor markers are carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and HCG. CEA cannot be used in screening for cancer, but in carcinoma of the colon its elevation preoperatively increases the likelihood of advanced disease and postoperative recurrence. Postoperatively, elevated titers are often but not invariably associated with recurrent disease. AFP and HCG are useful in the management of nonseminomatous germ cell testicular tumors. Like CEA, they cannot be used for screening. They are more likely to be increased with advancing stage, and after therapy rising levels almost always mean recurrent disease. Some markers are valuable in specific circumstances, such as calcitonin in screening for familial medullary carcinoma of the thyroid. In multiple myeloma, immunoglobulins are useful in determining the tumor mass and response to therapy. In neuroblastoma, catecholamine metabolites are useful primarily in making the diagnosis. In some malignancies, the absence of effective therapy lowers the value of the marker, as for AFP in hepatoma. The remaining markers are too unreliable or too little studied to be useful in the management of an individual patient with cancer. The purpose of this paper is to provide the clinician with an understanding of the limitations of the present tumor markers that will lead to wiser use of the tests, and to provide standards to which future tumor markers should be measured.
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PMID:Tumor markers: value and limitations in the management of cancer patients. 241 41

Four hybridomas secreting monoclonal antibodies (MAbs) of the IgG1 subclass against human carcinoembryonic antigen (CEA) were obtained from fusion of P3-NS1/1-Ag4 myeloma cells with splenic cells from mice immunized with purified CEA. None of the MAbs showed cross-reactivity to perchloric acid extractable antigens from the normal human colon by an inhibition radioimmunoassay. However, MAb C27 showed the highest affinity to CEA. The intensity of immunofluorescence staining of human colorectal cancer cells with MAb C27 correlates well to the cellular CEA content of cancer cells. LS174T showed the highest intensity of fluorescence (95%) while COLO320DM and COLO320HRS were the lowest (0.5%). None of the normal human organs - colon, lungs, liver, spleen or kidneys-showed positive staining by immunoperoxidase anti-peroxidase (PA) techniques, while tissues from colorectal carcinoma (CRC), gastric carcinoma, hepatoma and lung cancer gave a positive rate of 100% (30/30), 96.6% (28/29), 32.1% (9/28) and 82.1% (69/84) respectively. Results suggest that MAb C27 can be used in immunodetection and radiolocalization of colorectal carcinoma.
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PMID:Immunological characteristics of monoclonal antibodies against human carcinoembryonic antigen (CEA). 241 36

To avoid the exclusive use of rodent monoclonal antibodies (MAbs) in patients for the detection of tumors by immunoscintigraphy and for radioimmunotherapy, swine MAbs were produced that are directed against carcinoembryonic antigen (CEA). Spleen cells from 2 pigs immunized with purified colon carcinoma CEA were fused with a nonsecreting mouse myeloma cell line by conventional methods, except that a particularly long immunization protocol and large amounts of spleen and myeloma cells were used. Of 1,200 growing hybrids tested, 20 were found initially to produce antibodies binding to radiolabeled CEA. Seven stable clones producing anti-CEA MAbs for more than 6 months were derived from these hybrids by repeated subcloning. The pig origin of the seven MAbs was demonstrated in a solid-phase CEA enzyme immunoassay where anti-pig immunoglobin (Ig) antibodies coupled to peroxidase gave a positive reaction while anti-mouse Ig antibodies were entirely negative. All swine MAbs were of the IgG isotype. Three anti-CEA MAbs showed no cross-reactivity with granulocytes, while four others gave various degrees of reactivity with different granulocyte glycoproteins. Competitive binding to CEA performed for two purified swine MAbs showed that they recognized two different epitopes. The affinity constants measured for these two MAbs by Scatchard plot on purified CEA were high (1.2 X 10(9) and 1.2 X 10(10) liter/mol). One of the MAbs was tested in vivo for tumor localization by injection, after radiolabeling, in nude mice bearing human colon carcinoma xenograft. High ratios of tumor to normal tissue were obtained with mean values of 10.5 for intact MAbs and of 26.8 for F(ab')2 fragments of the porcine MAb. The results showed that heterofusion with this particular protocol can be used to produce swine MAbs of high affinity and specificity for a well-defined tumor marker. These reagents may have an important clinical utility, particularly in patients who became sensitized to mouse immunoglobulins.
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PMID:Swine monoclonal antibodies of high affinity and specificity to carcinoembryonic antigen. 243 34

To identify tumor-associated antigens that may be immunogenic to man, human monoclonal antibodies (human mAb) were generated by fusing nonsecreting mouse myeloma cells with lymphocytes from regional mesenteric nodes of patients with adenocarcinomas of the colon. One IgG1 human mAb, designated as 14-31-10, was identified by its reactivity against human tumor xenografts. We have studied the reactivity of mAb 14-31-10 with formalin-fixed, paraffin-embedded specimens of human colon. A total of 86 cases were studied, including normal adult and fetal colons, adenocarcinomas of the colon, and a variety of colonic inflammatory diseases and preneoplastic lesions. Intense reactivity was found in 15 of 18 adenocarcinomas of the colon, but not in 10 specimens of normal adult or 4 specimens of fetal colonic mucosa. Interestingly, in four cases of carcinoma, reactivity was also observed in histologically normal mucosa situated 10 cm or more from the primary lesion. On the other hand, no staining was detected in any of the 16 inflammatory lesions. Of the 38 preneoplastic lesions, only 6 showed staining by the mAb: 1 of 5 benign tubular adenomatous polyps, 3 of 9 villous adenomas and tubovillous polyps, 1 of 5 specimens of ulcerative colitis and 1 of 19 specimens of familial polyposis. However, the intensity of staining was only moderate in those cases. Our data, therefore, suggest that the epitope identified by the human mAb 14-31-10 shows preferential expression in preneoplastic and neoplastic lesions of the colon, and in ostensibly normal mucosa at some distance from a primary colonic carcinoma. In all instances, the staining was cytoplasmic, suggesting a cytoplasmic or internal membrane location of the target antigen. This antigen appeared to be distinct from carcinoembryonic antigen, since staining by 14-31-10 was consistently different from that of a mouse monoclonal antibody to carcinoembryonic antigen in serial sections of the same specimens. The restricted reactivity of 14-31-10 suggests its potential application in immunohistochemistry. Moreover, the epitope identified by mAb 14-31-10 may be expressed during the progression of normal mucosa to neoplasia.
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PMID:Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon. 246 41

Four monoclonal antibodies (MoAbs) reactive with carcinoembryonic antigen (CEA) were obtained by hybridizing mouse myeloma cells (P3-X63-Ag8-U1) with spleen cells from nude mice (BALB/c, nu/nu) that had rejected transplanted human colonic adenocarcinomas Co-3 and Co-4 following intraperitoneal injection of spleen cells from immunocompetent mice (BALB/c). By solid-phase RIA with purified CEA and its related antigens, NCC-CO-413 (IgG2a, kappa) was shown to react with NCA and BGP-I as well as with CEA, whereas the reactivities of three other MoAbs, NCC-CO-308 (IgG1, kappa), -432 (IgG1 lambda), and -411 (IgG1, kappa) were limited to CEA. Immunohistochemical reactivities of these MoAbs to colonic carcinomas, granulocytes, and liver bile canaliculi on acetone-fixed paraffin-embedded sections ("AMeX" sections) confirmed the specificities of these MoAbs shown by the solid-phase RIA. By competition solid-phase RIA, the epitopes recognized by NCC-CO-308 and -432 were shown to be shared or located close to each other, whereas the other MoAbs were shown to recognize different epitopes. Thus, two epitopes specific to CEA and one shared by NCA and BGP-I as well as CEA were identified. Furthermore, reactivities of MoAbs with the two CEA-specific epitopes were easily abolished by heat denaturation or reduction of CEA, as revealed by solid-phase RIA and SDS-PAGE-immunoblotting, indicating that these two CEA-specific epitopes are based on the conformational structure of the CEA molecule.
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PMID:Conformational epitopes specific to carcinoembryonic antigen defined by monoclonal antibodies raised against colon cancer xenografts. 247 24

By fusion of mouse NS1 myeloma cells with splenocytes from a BALB/c mouse immunized with human melanoma cells, an IgG1 monoclonal antibody, designated as 140.72, was produced. By the mixed hemadsorption antibody binding assay, 140.72 was shown to react with 17 of 20 melanoma cell lines and with 5 of 14 carcinoma cell lines. This antibody also reacted with 3 of 3 normal melanocyte cultures in much lower titers. It did not react with any of 35 other normal and malignant lines, including neuroblastoma, glioblastoma, sarcoma, teratoma, fibroblast, and lymphoid cell lines. Absorption with fresh melanoma and carcinoma homogenates confirmed the results of direct tests. Fetal reactivity of antibody 140.72 was determined by positive absorption with 10 of 11 tissue homogenates derived from different fetuses of 10-16 weeks' gestation. The reactivity of this antibody was completely removed by absorption with a highly purified preparation of carcinoembryonic antigen (CEA) derived from a colon carcinoma. The antigenic activity was detected in the culture medium of reactive cell lines. Immunoprecipitation analyses of melanoma and carcinoma cells indicated that the antigenic determinant recognized by antibody 140.72 is on a glycoprotein with an apparent molecular weight of 95,000-150,000 common to both serologically reactive cell types. Additionally, a 200,000-molecular-weight glycoprotein corresponding to the CEA molecule was detected only on the reactive carcinoma cells. These data confirmed previous findings obtained with polyclonal anti-CEA antisera for the existence of shared CEA-related antigenic determinants on human carcinomas and melanomas and provided additional molecular characterization of these glycoproteins. Further characterization of the molecules bearing the antigenic determinant recognized by antibody 140.72 should be performed with a view to exploring its potential in the immunodiagnosis and immunotherapy of patients with melanoma.
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PMID:Monoclonal antibody recognizing human melanoma-carcinoma cross-reacting oncofetal antigen epitopically associated with carcinoembryonic antigen. 258 73

A procedure was devised for the identification and specific cloning of functionally rearranged variable region immunoglobulin (Ig) gene segments from genomic DNA of a murine hybridoma cell line which produces a high-affinity monoclonal antibody (MAb) directed against human carcinoembryonic antigen (CEA). The cloned, functionally-rearranged murine Ig H-chain and L-chain variable region gene segments were incorporated into plasmid vectors capable of directing the expression of a chimaeric mouse-human antibody molecule with human (gamma 4, kappa) constant region sequences. Expression plasmids were transfected into a mouse myeloma cell line by electroporation and transfectomas secreting functional chimaeric antibody selected. Chimaeric antibody generated by transfectomas was analysed and shown to compete effectively with its murine counterpart for binding to the CEA epitope, and to have an equivalent antigen-binding affinity. This anti-CEA recombinant antibody should find application in in vivo diagnosis by immunoscintigraphy of human colonic carcinoma, and possibly also in therapy of the disease, overcoming some of the difficulties associated with the repeated use of non-human immunoglobulins in human patients.
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PMID:Generation of a recombinant mouse-human chimaeric monoclonal antibody directed against human carcinoembryonic antigen. 277 9

Two monoclonal antibodies, designated 4C4 and 4G1, were produced by immunization of BALB/c mice with a human esophageal carcinoma cell line, CE69T/VGH, followed by fusion of the spleen cells from an immunized mouse with myeloma cells NS-1. 4C4 showed strong binding activity to three human esophageal carcinoma cell lines and one human hepatoma cell line, but not to any other cell lines tested. 4G1 reacted with three human esophageal carcinoma cell lines and four other cell lines. By peroxidase-antiperoxidase staining, 4C4 and 4G1 detected antigens of the epithelial cells on 10 pairs of esophageal carcinoma and normal esophageal specimens. 4G1 recognized a CE69T/VGH antigen with a molecular weight of 180K. Since 4G1 also reacted with purified carcinoembryonic antigen (CEA) and immunoprecipitated 125I-CEA, 4G1 seems to be an antibody recognizing CEA produced by CE69T/VGH cells. Since 4C4 also bound to the epithelial cells of normal uterine, vaginal, breast and liver tissues, it seems to recognize an epithelial antigen, and can be used to characterize the antigen in the specialization or differentiation of epithelial cells.
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PMID:Monoclonal antibodies against human esophageal carcinoma cell lines. 282 67

A mouse/human chimeric antibody has been constructed by using variable light and variable heavy regions from a murine hybridoma specific for human carcinoembryonic antigen (CEA) (CEM231.6.7). These V regions were combined with kappa and gamma-1 constant region genes cloned from human lymphocytes. The chimeric constructs were sequentially electroporated into murine non-Ig-producing myeloma (P3.653) and hybridoma (SP2/0) cell. Significant differences were seen in expression levels between the two cell types. High levels of expression (24 to 32 micrograms/ml/10(6) cells) were seen with several of the anti-CEA SP2/0 transfectomas but not with the P3.653 cells. The SP2/0 transfectoma lines were adapted to serum-free, chemically defined media and grown in large scale fermentation cultures where they continued to secrete high levels of antibody. The chimeric antibodies remain reactive against human CEA with affinity constants comparable to that of the parental hybridoma antibody. High level expression will make practical the production of chimeric antibodies for in vivo therapeutic and diagnostic purposes.
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PMID:Cloning and high level expression of a chimeric antibody with specificity for human carcinoembryonic antigen. 314 12


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