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)

A monoclonal antibody was prepared by hybridizing mouse myeloma cells with spleen cells from the mouse which was immunized with human colon cancer transplanted in nude mice. The reactivity of the monoclonal antibody, named A7, was tested by immunoperoxidase method. A7 reacted strongly with human adenocarcinoma cell lines and carcinoembryonic antigen (CEA). In surgical specimens, A7 reacted with 10 cancer tissues and 2 normal colon mucosa from 19 colorectal cancer patients. A7 did not react with other cancers. It was thought that A7 reacted with colon- or colon cancer-specific CEA. The reactivity of A7 with colorectal cancers was markedly reduced by preoperative irradiation.
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PMID:A monoclonal antibody against human colon cancers. 352 36

The simultaneous distribution of monoclonal 131I-labeled anti-carcinoembryonic antigen (CEA) immunoglobulin (IgG) (NP-2) or 131I-labeled irrelevant myeloma IgG (Ag8) and [3H]thymidine was studied in hamsters bearing transplants of the GW-39 human colon carcinoma by qualitative double-tracer whole-body autoradiography. Autoradiography showed that large solid GW-39 tumors are characterized by heterogeneity of radioantibody retention and uneven [3H]thymidine accumulation, reflecting zonal variations in antibody reactivity and tumor cell proliferation, respectively. The autoradiographic images showed that both 131I-labeled-monoclonal antibody and control 131I-labeled IgG targeted nonproliferating tumor zones, suggesting a mechanism of nonspecific tumor uptake of radioantibodies in these areas. Absence of tumor center labeling with [3H]thymidine, associated with cellular necrosis, was confirmed by histology and microautoradiography in separate animal studies. In confirmation of earlier reports, 131I-labeled anti-CEA monoclonal antibody gave higher tumor-to-non-tumor labeling patterns than did control 131I-labeled IgG, at both 3 and 7 days following treatment. Immunohistochemical localization of CEA in GW-39 tumors with necrotic centers showed the presence of CEA in nonviable cells, but CEA antigen concentrations were diminished as compared to cells located in the tumor's periphery. The results indicate that double-tracer whole-body autoradiography is well suited for studying the kinetics of radioantibody localization in relation to regional tumor cell viability.
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PMID:Relationship of radioantibody localization and cell viability in a xenografted human cancer model as measured by whole-body autoradiography. 354 50

To analyze the humoral immune response to melanoma, human-mouse hybridomas were generated by the fusions of regional lymph node lymphocytes of patients with the mouse myeloma cell line M5. Six stable hybridomas were cloned from six separate lymphocyte parents obtained from three patients. Ascites were obtained from nude mice after i.p. injection with cultured hybridoma cells. The monoclonal antibodies, four immunoglobulin Gs and two pentameric immunoglobulin Ms, were partially purified to remove mouse immunoglobulin and then conjugated to biotin for immunocytochemical and immunohistochemical studies. With the avidin:biotin:peroxidase complex method to detect and amplify binding by the biotin-conjugated human monoclonal antibodies, we found the six antibodies to be reactive against cytoplasmic determinants in five short-term melanoma cultures and formalin-fixed paraffin-embedded melanoma tumors from four patients. The antigenic target of the antibodies identified was not carcinoembryonic antigen. Two antibodies, 2-139-1 and 6-26-3, were studied in more detail. Each stained 25 of 25 specimens of melanomas. Little or no reactivity was detected against fixed sections of normal skin, which included tissues such as epidermis, dermis, monocytes, lymphocytes, and vascular endothelium. More striking was the absence of binding to melanocytes in the basal layer of the skin or to pigmented nevus cells. Both antibodies showed cross-reactivity against other tumors, in particular colonic and prostatic carcinomas. In the normal colon, reactivity was restricted to the surface of the columnar epithelium; no reactivity was detected against normal prostatic epithelium. Reactivity was also not observed against liver and lung. However, the epithelia of the renal tubules, pancreatic ducts, and salivary ducts were all reactive. These human monoclonal antibodies identify cytoplasmic melanoma-associated tumor antigens that appear different from the membrane antigens defined by serological approaches and by most mouse monoclonal antibodies.
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PMID:Human monoclonal antibodies directed against melanoma tumor-associated antigens. 369 90

Spleen cells from mice immunized with purified carcinoembryonic antigen (CEA), an important tumor marker of human carcinomas, were fused with the mouse myeloma cell line P3-NSI/1-Ag4. Out of the 400 hybrids obtained, 2 secreted antibodies reacting specifically with two different antigenic determinants present on CEA molecules. They were cloned and established as permanent hybridoma cell lines. These antibodies, which have relatively high-affinities and can be produced in unlimited amounts, will be useful both for the immunochemical characterization of CEA and as a standard reagent for the identification of this antigen in human tissues and body fluids.
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PMID:Monoclonal antibodies specific for carcinoembryonic antigen and produced by two hybrid cell lines. 615 97

Spleen cells from BALB/c mice immunized with human ovarian cystadenocarcinoma extract were fused with the mouse myeloma cell line P3/NSI/1-Ag 4 in the presence of polyethylene glycol (Mr 4000). Of the 46 hybrids obtained, four secreted antibodies preferentially reactive to the immunizing ovarian tumor extract. Two of these hybrids, which showed no reaction with normal controls, were selected for cloning by the limiting dilution method. The numerous clones obtained from each hybrid were screened against a panel of five ovarian tumor extracts, pooled normal ovary extracts, and pooled normal human sera. One clone from each hybrid that showed specificity for ovarian mucinous cystadenocarcinomas was recloned to assure monoclonality and to establish a permanent hybridoma cell line. The antibodies secreted by these cell lines were of IgG1 subclass with kappa light chains. These antibody-producing hybridomas were selected for further analysis of the antibody specificity by a solid-phase radioimmunoassay and quantitative absorption tests. The monoclonal antibodies recognized an antigenic determinant present only in mucinous cystadenocarcinomas of the ovary. These did not react with any other gynecological or nongynecological tumor thus far tested. The antigen was not demonstrable in any normal adult tissues tested. Among fetal tissues examined, only fetal intestine extract showed a positive reaction. The antigenic determinant recognized by these monoclonal antibodies was unrelated to carcinoembryonic antigen, normal glycoprotein, normal human serum components, or human ABO blood group materials. These antibodies, which have relatively high affinity and can be produced in large amounts, will be useful for the isolation and immunochemical characterization of this antigen. The purified antigen and the specific antibodies could be then combined in a sensitive radioimmunoassay for the early detection of the antigen in the sera and body fluids of patients with ovarian mucinous cystadenocarcinomas.
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PMID:Monoclonal antibodies recognizing tumor-associated antigen of human ovarian mucinous cystadenocarcinomas. 617 95

By fusion of C3H mouse spleen cells, immunized with a PCA extract from liver metastases of a colon tumor, and Sp2/O-Ag14 myeloma cells, we produced several clones secreting monoclonal antibodies (MAb) with reactivity against carcinoembryonic antigen (CEA). For the screening of the different MAb, an ELISA technique with PCA extract and highly purified CEA coupled with alkaline phosphatase was employed. The specificities of the MAb prescreened with the ELISA technique were analyzed further by immunoprecipitation and separation on SDS-PAGE, followed by enzyme digestion and thin-layer chromatography for fingerprint analysis. The MAb recognized (a) an antigenic determinant present only on CEA, (b) common determinants present on CEA and at least six other molecules separated by SDS-PAGE and (c) antigenic determinants not present on CEA. The fingerprint analysis showed the relationship of the molecules on the basis of protein chemistry.
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PMID:Monoclonal antibodies against CEA. Comparison of the immunoprecipitates by fingerprint analysis. 618 85

A systematic approach for the determination of epitope specificities of monoclonal antibodies to a complex antigen system is described. After initial screening to identify antigen-binding monoclonal antibodies, one or more of the clones are isolated by limiting dilution cloning, grown in ascites, and the resulting antibodies secreted into the ascitic fluid are affinity purified on Sepharose-bound protein A, radiolabeled, and cross-compared with antibodies from other clones by a solid-phase competitive immunoassay. In this work, BALB/c mice were immunized with either purified carcinoembryonic antigen (CEA) or the CEA-producing cell line HC 84S. Spleen cells were fused with the mouse myeloma cell line Sp2/0-Ag14. The supernatants from 25 hybrids showed a significant binding of 125I-CEA (greater than or equal to 15%). Nine hybrids were cloned, resulting in 33 different clones. The antibodies produced by the different cloned hybrids and the remaining uncloned hybrids recognized a total of five different epitopes on CEA. All of the epitopes reside on the protein moiety of the molecule as determined by antibody binding to deglycosylated CEA. The monoclonal antibodies with five different epitope specificities were reacted with tissue sections of normal and cancerous tissues and with peripheral blood smears. Each of the five monoclonal antibodies reacted with tissue sections from colonic, gastric, lung, and mammary carcinomas, as well as from a benign colonic polyp and a resection margin from a colonic carcinoma. Four monoclonals reacted with normal liver tissue. Granulocytes in peripheral blood smears bound three antibodies strongly and one antibody weakly, and one antibody was not bound. One monoclonal antibody that reacted with normal liver tissue was not bound by granulocytes. The ability of these five monoclonal antibodies to differentially detect three different CEA-related antigens in normal and malignant tissues may have clinical utility.
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PMID:Monoclonal antibodies for carcinoembryonic antigen and related antigens as a model system: a systematic approach for the determination of epitope specificities of monoclonal antibodies. 618 49

Eleven hybridoma clones producing monoclonal antibodies to carcinoembryonic antigen (CEA) were prepared by fusions of the mouse myeloma cell line P3-X63-Ag8-U1 with splenocytes of BALB/c mice immunized with highly purified CEA. Their specificities were systematically analyzed by radioimmunoassay for reactivity with CEA and four related normal antigens: nonspecific cross-reacting antigen (NCA), nonspecific cross-reacting antigen-2 (NCA-2), normal fecal antigen-1 (NFA-1), and normal fecal antigen-2 (NFA-2). Antibody-antigen profiles revealed four groups of hybridomas. The Group I antibodies from two clones reacted with sites shared among CEA, NCA, NCA-2, and NFA-2. The Group II antibody from one clone recognized an epitope common to CEA, NCA-2, and NFA-2. The Group III antibodies from five clones reacted with sites commonly residing on CEA, NCA-2, NFA-1, and NFA-2, whereas antibodies of Group IV from three clones bound only CEA. Mutual inhibition assays between antibodies in the respective groups for CEA binding further revealed that at least eight different epitopes can be identified on the CEA molecule: two in Group I, one in Group II, three in Group III, and two in Group IV, respectively. Three monoclonal antibodies in Group IV appeared to be specific for CEA, but they did not react with any of five purified CEA preparations other than that used for immunization. In 13 sera from 50 various cancer patients with elevated CEA levels, however, we detected the CEA molecule reactive with these antibodies, indicating that the epitopes recognized by the Group IV antibodies may be of allotypic characters. These epitopes were unrelated to main blood group antigens and did not show any organ specificity. All of the eight epitopes identified in this study were found to be resistant to neuraminidase, mixed glycosidases, and Smith degradation (SI-stage) as determined by a competitive radioimmunoassay, suggesting that they reside on the protein moiety of the CEA molecule. Six epitopes were sensitive to reduction and alkylation, but two other epitopes (one in Group II and the other in Group III) were resistant to these treatments. This result indicates that the latter two epitopes are conformation-independent.
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PMID:Monoclonal antibodies to carcinoembryonic antigen: a systematic analysis of antibody specificities by using related normal antigens and evidence for allotypic determinants on carcinoembryonic antigen. 620 51

Splenic lymphocytes of mice immunized with membrane enriched fractions of human mammary carcinomas were fused with the NS-1 nonsecretory++ myeloma cell line. The resulting hybridomas were screened for the synthesis of immunoglobulins reactive with human mammary tumor associated antigens, and two IgG monoclonal antibodies (B1.1 and F5.5) were identified as being reactive with purified carcinoembryonic antigen (CEA). These antibodies were shown to bind to different epitopes on CEA based on their differential reactivities to five different purified CEA preparations, and their differential binding to the surface of tumor cells derived from various organ sites. Monoclonal B1.1 bound equally to the surface of human breast, colon, and melanoma cell lines. Monoclonal F5.5, on the other hand, did not react with the surface of melanoma cell lines, and showed a differential binding to breast carcinoma versus colon carcinoma cells. Monoclonals F5.5 and B1.1 were both used in immunoperoxidase studies with fixed tissue sections of a variety of histologic types of human mammary carcinomas and were shown to be reactive with 55% and 66%, respectively, of tumor masses.
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PMID:Differential binding to human mammary and nonmammary tumors of monoclonal antibodies reactive with carcinoembryonic antigen. 636 68

Monoclonal antibodies were produced by immunizing BALB/c mice with a human lung squamous carcinoma line (UCLA-SO-P3) or with freshly obtained lung carcinoma cells and by fusing the immunized splenocytes to mouse myeloma S194. Six monoclonal antibodies were selected after testing the reactivity to a panel of human tumors and non-tumors by an indirect 125I-protein A binding assay, a complement dependent microcytotoxicity assay or an immunofluorescence assay. As a result, four types of antigens were identified. MoAb 169D4 is of IgM class and reacted only to P3 lung carcinoma and to one of the colon carcinomas. This antibody actually possessed the A1 Lewis d specificity. MoAb 172D5 reacted to 8 out of 11 carcinomas but did not react to other types of tumor or lymphoid cells while detecting a carcinoma-associated antigen. MoAb 170C5, 754A3 and 806B4 reacted to carcinomas and embryonic cells, but detected antigenic determinants other than the carcinoembryonic antigen. By means of a protein antigen analysis using immunoprecipitation and SDS-polyacrylamide gel electrophoresis, MoAb 170C5, 754A3 and 806B4 detected molecular weights of 130,000, 55,000, and 135,000, respectively. MoAb 169F3 reacted to all the tested carcinomas, sarcomas, and melanomas, and some of the leukemias. This antibody also reacted to human peripheral monocytes and platelets and was shown to detect an antigen widely distributed among tumors and parts of normal cells.
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PMID:Analysis of cell surface antigens expressed on a human lung carcinoma by monoclonal antibodies. 662 11


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