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M J Mattes

Publications and source records attributed to M J Mattes.

At least 73 records · Page 4Linked to original sources
PubMed1987

Monoclonal antibody to an intracellular antigen images human melanoma transplants in nu/nu mice.

Mouse monoclonal antibody TA99 detects a 70-kDa pigmentation-associated glycoprotein in human melanoma cell lines. The antigen cannot be detected on the cell surface by sensitive rosetting techniques or absorption studies, nor can it be detected as a secreted product in culture fluids. Contrary to expectation, 125I-labeled TA99 specifically localized to pigmented human melanoma transplants in nu/nu mice; no localization to nonpigmented melanoma or control tumors was found. Tumor imaging was initially obscured by circulating 125I-labeled TA99 during the first 6 days after antibody injection. With clearance of 125I-labeled TA99 from the blood (half-life, 4-7 days), specific tumor images could be clearly defined by day 13. Due to the persistence of 125I-labeled TA99 at the tumor site (8.9% of the injected dose at 1 week and 4.6% at 8-10 weeks), images were obtainable for up to 10 weeks. At 8-10 weeks, the tumor/blood ratio was 10(4)-10(5), and the tumor/normal tissue ratio ranged from 10(2) to 10(5). In view of these findings, antibodies detecting intracellular antigens may have a role in tumor imaging and therapy.

Animals↗
PubMed1987

Biodistribution of antibodies after intraperitoneal or intravenous injection and effect of carbohydrate modifications.

These studies were designed to improve the strategy for intraperitoneal immunotherapy of human ovarian carcinoma with monoclonal antibodies (MAbs). Since ovarian tumor cells generally appear to be confined to the peritoneal cavity, regional therapy is appropriate and can reduce the need for strictly tumor-specific MAbs. In normal mice, with the use of radioiodine-labeled MAbs, transfer from peritoneal cavity to blood was found to be very rapid, within hours, and this transfer was delayed slightly by increasing the volume injected. The presence of ascitic fluid in mice greatly delayed the rate of transfer. For reduction of possible toxicity for normal cells outside the peritoneal cavity, the hepatic receptor for desialylated serum glycoproteins was used. Neuraminidase treatment of all major mouse immunoglobulin classes and subclasses, including IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA, did not cause their rapid blood clearance, although similar treatment of fetuin was effective. Conjugation of IgG with galactose, with use of the cyanomethyl derivative, did result in very rapid blood clearance via the hepatic lectin; within 3 minutes clearance was essentially complete. The specificity of uptake was demonstrated by inhibition with desialylated fetuin. Degradation within the liver, release of the radioiodine, and excretion from the animal were also quite rapid, within hours. This conjugation procedure had no effect on the antibody activity of the two MAbs tested. Such modified MAbs, therefore, are degraded almost immediately after entering the blood and would be advantageous in intraperitoneal therapy and in other situations in which regional immunotherapy is appropriate.

Animals↗
PubMed1986

Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype.

We have used serologic, biochemical, and genetic methods to characterize two stage-specific human differentiation antigens of neural and melanocytic cells: A42 (57,000 Mr glycoprotein) and J143 (140,000/30,000 Mr glycoprotein). The genes determining A42 and J143 cell surface expression in rodent-human hybrids were chromosomally mapped, and the respective human chromosomes were introduced into rodent cells derived from distinct differentiation lineages. Serologic analysis of the resulting hybrid clones has permitted the identification of two types of regulatory signals determining A42 and J143 expression. First, both antigens are expressed in hybrids constructed with antigen-positive human cells and also in certain hybrids constructed with antigen-negative human cells, indicating that intrinsic signals provided by the differentiation program of the rodent fusion partner induce antigen expression. Second, a series of human-mouse neuroblastoma hybrids, which are A42- or J143- when cultured on plastic surfaces, can be induced to express the antigens when cultured on substrates coated with extracellular matrix (ECM) produced by bovine corneal endothelial cells or fibronectin. This induction of antigen expression by extrinsic, ECM-derived signals is accompanied in the neuroblastoma hybrids by increased substrate adhesiveness and cell spreading and by characteristic changes in cell morphology. A similar program of phenotypic changes is also seen in spontaneous variants of human neuroblastoma and Ewing's sarcoma cells and in ECM-induced Ewing's sarcoma cells. These findings suggest that ECM-derived signals have a role analogous to mitogens and soluble differentiation factors in modulating differentiation phenotypes and tissue-specific patterns of cell surface antigen expression.

Antibodies, Monoclonal↗
PubMed1985

Analysis of the specificity of five murine anti-blood group A monoclonal antibodies, including one that identifies type 3 and type 4 A determinants.

The specificity of five mouse monoclonal anti-A blood group antibodies (Ab), four of which were produced by immunization with cultured human cancer cells and one with a synthetic antigen, has been determined by examining their reactivity with purified A glycolipids, erythrocyte glycolipids, oligosaccharides, ovarian cyst glycoproteins, and salivary glycoproteins. Two of the antibodies (HT29-36 and CB) reacted with all A variant structures tested and have a broad anti-A reactivity. Ab CLH6 did not agglutinate A erythrocytes and reacted preferentially with the type 1A structure. Ab S12 agglutinated all A1 erythrocytes and reacted best with simple, monofucosyl type 2 A structures, such as Aa-2, Ab-2, and A tetrasaccharide. Ab M2 has a novel, but complex, spectrum of reactivity. It reacts with type 3 and type 4 A chains and not with type 1 and type 2 A chains. It appears to recognize both an external A structure (formula; see text) (I) (found) in type 3 and type 4 chains) and also an internal structure (II) found in type 3 chains. Ab M2 agglutinates all A and AB erythrocytes but does not react with salivary glycoproteins.

ABO Blood-Group System↗
PubMed1985

Immunopathologic analysis of a panel of mouse monoclonal antibodies reacting with human ovarian carcinomas and other human tumors.

The reactivity of a panel of five mouse monoclonal antibodies (mAb) produced to human ovarian and endometrial cancer cell lines was analyzed on frozen sections of normal adult and fetal tissues and on tumor sections using immunofluorescence and immunoperoxidase procedures. mAb MH99 was reactive with almost all types of epithelial cells and stained all epithelial tumors examined. mAb MH94 reacted mainly with secretory epithelia and was unreactive with the epithelial cell layer of normal ovaries. In contrast, approximately 50% of epithelial ovarian tumors and the lining cells of inclusion cysts were positive. mAb MF61 was positive only on the endometrium and noncellular follicular secretions or colloid of the thyroid among normal tissues examined. A subset of ovarian tumors was positive with this antibody. mAb MF116 gave no reactivity with normal tissues within the sensitivity of the assay. MF116 was expressed on a proportion (44%) of ovarian carcinomas of various histological types. These antibodies provide an initial panel for the immunohistological analysis of ovarian cancer.

Animals↗
PubMed1985

Pigmentation-associated glycoprotein of human melanomas and melanocytes: definition with a mouse monoclonal antibody.

Pigmented melanoma cells and cultured melanocytes express a differentiation-related glycoprotein designated as pigmentation-associated antigen (PAA) of Mr 70,000-80,000. As described previously, PAA was initially defined by reactivity with antibodies in the serum of a patient with melanoma. Here we describe the production and characterization of a mouse monoclonal antibody to PAA. This antibody (TA99, an IgG2a) was shown by sequential immunoprecipitation experiments to react with the same component as the human antibody. Ab TA99 immunoprecipitated PAA from lysates of cells radiolabeled with [35S]methionine, [3H]glucosamine, [3H]fucose, and [3H]mannose as well as 125I. Using Ab TA99, the distribution of PAA was examined in frozen sections of 19 normal tissues and quantitatively in 68 tissue culture cell lines. In frozen sections, only melanin-containing cells were positive, including epithelial cells in the basal layer of the epidermis, in which pigment originates from melanocytes by transfer of melanosomes, and pigmented cells of the eye. In tissue culture cell lines, only pigmented melanoma cells were positive. PAA is an intracellular antigen, with a distribution very similar to that of melanosomes. This evidence confirms the close association of PAA with melanin production, and suggests that PAA may be a melanosome component. PAA was shown to be different from tyrosinase, the enzyme involved in melanin synthesis, but it was found to be identical to the previously recognized glycoprotein, gp75, characteristic of pigmented melanomas and melanocytes.

Animals↗
PubMed1985

Three mouse monoclonal antibodies to human differentiation antigens: reactivity with two mucin-like antigens and with connective tissue fibers.

Three human differentiation antigens (MU78, MT334, and MQ49) have been defined by mouse monoclonal antibodies developed from mice immunized with ovarian carcinoma cell lines. Their distribution was determined on 148 cultured cell lines of various histologic types and on frozen sections of 16 normal tissues. MU78 was found in fibrillar structures in soft connective tissue with a distribution resembling that of elastin fibers; however, elastin fibers in elastic cartilage and in the aorta were nonreactive. MU78 was detected in cultured carcinoma cells of various histologic types, where it had a nonfibrillar, cytoplasmic distribution, but was not detected in normal epithelial cells in frozen sections. Cultured fibroblasts, astrocytomas, melanomas, and lymphomas did not contain MU78. In cell lines, MU78 appears to be a protein of 2000-5000 daltons. The other two antigens, MT334 and MQ49, are both mucin-like molecules, and the determinants are probably carbohydrate in nature. Of the normal tissues examined, MT334 was detected only in goblet cells of the colon, though it was present in a variety of carcinomas in culture. It was detected as both a cytoplasmic and secreted component. MQ49 was detected in various secretory epithelial cells, in Hassall's corpuscles in the thymus, and in cultured carcinomas of various histologic types. It was found on the cell surface as well as in the cytoplasm and is present on a glycolipid as well as on a sulfated mucin. These results, and results of other recent studies, demonstrate the importance of mucin-like molecules as antigens in epithelial cells and secretions.

Animals↗
PubMed1985

A1 and A2 erythrocytes can be distinguished by reagents that do not detect structural differences between the two cell types.

The differential reactivity of four mouse monoclonal antibodies (AbCB, AbHT29-36, AbM2, and AbS12) and Dolichos biflorus lectin with A1 and A2 erythrocytes was analyzed. Only AbS12 and D. biflorus lectin were able to preferentially agglutinate A1 erythrocytes. AbS12 is known to react only with short chain, unbranched structures (such as Aa-2 and Ab-2 glycolipids) and not with longer chains or with type 3 and type 4 structures. D. biflorus was shown to have a similar specificity by lectin staining of glycolipids separated by thin-layer chromatography. Analysis of the binding of radiolabeled AbCB and AbS12 to A1 and A2 erythrocytes by Scatchard analysis showed that, whereas the former antibody recognizes high-affinity sites on both A1 and A2 cells, AbS12 reacts with high-affinity sites only on A1 cells. Because A1 and A2 erythrocytes have a similar complement of short chain type 2 glycolipids, although in different amounts, it is suggested that AbS12 and D. biflorus lectin differentiate between the two cell types on the basis of quantitative, nonstructural features. This is in contrast to AbTH1, which reacts with a repetitive A epitope (type 3 A chain) and distinguishes between A1 and A2 cells based on the preferential expression of type 3 A chains in A1 erythrocytes. Thus, two views of A1/A2, i.e., qualitative vs quantitative are correct, depending on the properties of the reagent being used to distinguish between the two cell types.

ABO Blood-Group System↗
PubMed1984

Class 1 (unique) tumor antigens of human melanoma. Identification of a 90,000 dalton cell surface glycoprotein by autologous antibody.

Analysis of the humoral immune response of patients with melanoma has identified a small group of individuals with antibody to cell surface antigens that are restricted to autologous melanoma cells. These antigens, referred to as Class I or unique tumor antigens, are demonstrated by reactions between serum and cultured melanoma cells from the same patient and absorption tests with autologous and allogeneic normal and malignant cells to determine antibody specificity. Five Class 1 melanoma antigens have been defined to date, but insight into the nature of these antigens has been limited because antibodies identifying these antigens lacked detectable immunoprecipitating activity. We have now defined a Class 1 melanoma antigen (designated FD) that is immunoprecipitated by autologous antibody. FD antigen is identified by an IgG antibody present in the sera of patient FD, and peak titers of this antibody in tests with cultured autologous melanoma cells are in the range of 1:2048. By absorption tests, FD antigen could not be detected on any other cell type, including 33 allogeneic melanomas. Prolonged culture of FD melanoma cells resulted in decreased expression of FD antigen, but sublines could be obtained with stable antigen expression. FD antigen is trypsin and heat sensitive, neuraminidase resistant, and is shed in the culture medium. Immunoprecipitation of 125I-labeled cell membrane preparations revealed a 90,000 dalton component of pI 5.5. Serum immunoprecipitating activity could be absorbed by autologous melanoma cells but not by autologous B cells or allogeneic cell lines. A component of the same molecular mass could be precipitated from lysates of cells metabolically labeled with [3H]mannose. The membrane form of the FD antigen binds strongly to Con A-Sepharose and can be eluted with methyl-alpha-D-mannoside. The identification of a precipitating Class I antigenic system of melanoma facilitates efforts to generate monoclonal antibodies to this tumor antigen and to clone its coding sequence.

Absorption↗
PubMed1984

Cell surface antigens of human ovarian and endometrial carcinoma defined by mouse monoclonal antibodies.

Mouse monoclonal antibodies to several cell surface antigens of human ovarian and endometrial carcinomas have been produced. The distribution of the antigens was determined by mixed hemagglutination assays on 153 normal and malignant cell cultures of various types and by immuno-peroxidase staining of frozen sections of 27 normal adult and 24 fetal tissues. Five distinct antigens were characterized. MD144 antigen was detected on only a single ovarian carcinoma cell line and has the biochemical properties of a lipid. MH55 antigen is weakly expressed on ovarian and uterine cancer cell lines but not on other cells and tissues tested. MF61 antigen was detected on an ovarian carcinoma and some renal carcinoma cell lines but not on other cell lines tested. It was also detected by immunoperoxidase staining in the noncellular follicles of the thyroid and in uterine glandular epithelial cells. This antigen also has the properties of a lipid. MF116 antigen was detected on a proportion of ovarian, uterine, renal, and bladder carcinoma and neuroblastoma cell lines and on normal kidney epithelial cell cultures but not on other cell lines tested. It was not detected in sections of any normal tissue tested using the immunoperoxidase method. MF116 was readily detected in the spent culture medium but not in detergent-solubilized extracts of metabolically radiolabeled cells. This shed antigen is a glycoprotein of Mr 105,000 and isoelectric point lower than pH 4.0. MH94 antigen was detected on a proportion of ovarian, uterine, colon, breast, lung, cervical, and pancreatic carcinoma cell lines. In tissue sections it was detected in many but not all epithelia, predominantly in secretory epithelial cells. Antibody MH94 did not immunoprecipitate a detectable antigen.

Antibodies, Monoclonal↗
PubMed1983

A pigmentation-associated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum.

Antibodies in the serum of melanoma patient AU precipitate an antigen from 125I-labelled extracts of cultured autologous melanoma cells. The antigen, which is probably not a cell surface component, is present in other pigmented melanomas but not in non-pigmented melanomas or other tumor cell types, and the amount of antigen is correlated with the degree of pigmentation. These conclusions are based on absorption experiments with 11 pigmented melanomas, 8 non-pigmented melanomas, 3 astrocytomas, 12 carcinomas of various histological types, I leukemia, 2 EB-virus-transformed B lymphocyte lines, and human erythrocytes. The antigen was also detected in cultured human melanocytes. It has a molecular weight of 70,000, an isoelectric point of pH 5.3, and it binds to concanavalin A-Sepharose. Ninety-six sera from other melanoma patients were examined and none of them precipitated this antigen. As described previously, the serum from patient AU also has antibodies to a unique (Class I) tumor antigen found only on AU melanoma cells. The pigmentation-associated, differentiation antigen and the unique antigen are clearly different in their distribution, but some relationship between these unusual antibody responses is possible.

Antibodies, Neoplasm↗
PubMed1983

Preparing monolayers of non-adherent mammalian cells.

A simple method is described for preparing monolayers of non-adherent cells, using concanavalin A to bind the cells to wells of plastic microtest plates. The method was used successfully with all 202 human cell types tested, which included 23 tissue culture lines, 165 fresh specimens of all major histological types of leukemia and lymphoma, 20 fresh myelomas, 2 fresh thymomas, normal spleen and lymph node cells, fractionated T lymphocytes and B lymphocytes from peripheral blood, and cultured fetal amniotic cells. All cell types attached firmly, and were not detached by subsequent vigorous washing. In contrast, attempted attachment of cells in serum free medium, or with poly-L-lysine or glutaraldehyde, was ineffective with many cell types. We used the monolayers as target cells for antibodies to cell surface antigens, utilizing immune rosetting or complement-mediated cytotoxicity. This procedure should simplify most assays involving non-adherent target cells.

Amniotic Fluid↗
PubMed1983

Monoclonal antibodies to three widely distributed human cell surface antigens.

Four mouse monoclonal antibodies to widely distributed human cell surface antigens are described. The AJ2 antigen is one of the immunodominant antigens in mice immunized with human cells, as demonstrated by testing conventional mouse antisera. This antigen has four subunits having molecular weights (MW) of 170 kD, 140 kD, 140 kD, and 28 kD when immunoprecipitated from the immunizing cell line, an astrocytoma. With other cell lines the molecular weights and subunit composition varies, but the major component is always of MW 125-140 kD. The antigen was detected on all human tissue culture cells and on sections of all normal human tissues tested. Antibody MA99 detects the same antigenic complex but shows a slightly different pattern of reactivity with cell lines and tissues. The MA103 antigen has a similar ubiquitous distribution. It is a glycoprotein of MW 50-55 kD and the determinant detected is not denatured by treatment at 100 degrees C. MH99, the third common antigen detected, has two glycosylated subunits with MW of 29 kD and 38 kD. It is present on a subpopulation of tumor cell lines of most histologic types except that it is absent or weakly expressed on melanomas and astrocytomas. MH99 is present on some T lymphomas and leukemias and myeloid leukemias but was not detected on B lymphomas, null cell lymphomas and myelomas. It was detected preferentially on epithelial cells in tissue sections.

Animals↗
PubMed1982

Cell surface antigens of human astrocytoma defined by mouse monoclonal antibodies: identification of astrocytoma subsets.

The surface antigens of cultured human malignant astrocytomas were analyzed by using mouse monoclonal antibodies. BALB/c mice were immunized repeatedly with either SK-MG-1 [a glial fibrillary acidic protein (GFA)-negative astrocytoma line] or SK-AO2 (a GFA-positive astrocytoma line). After fusion with NS/1 mouse myeloma cells, 12 antibody-producing clones were selected for detailed study. Serological analysis permitted the identification of nine distinct antigenic systems. Four monoclonal antibodies (Ab AJ225, Ab AO10, Ab AJ8, and Ab AO122) identified cell surface antigens preferentially expressed on tumors of neuroectodermal origin, and these antibodies subdivided the astrocytoma panel into distinguishable subsets. The determinant detected by Ab AO10 and Ab AJ8 showed mutually exclusive expression on the astrocytoma lines. The AO10 and AJ8 phenotypes appeared to reflect the differentiation state of the cultured cells; 4/7 AO10-positive astrocytomas expressed GFA, an intracellular astrocyte differentiation antigen, whereas all AJ8-positive astrocytoma (9/9) were GFA-negative. Five antibodies (Ab AJ10, Ab AJ9, Ab AJ17, Ab AJ425, and Ab AJ2) recognized determinants widely distributed on normal and malignant cells. Four antibodies defined in this study precipitated proteins from reduced preparations of radioisotope-labeled SK-MG-1 and SK-AO2 cells: Ab AJ225 (Mr 145,000); Ab AO122 (Mr265,000); Ab AJ10 (Mrs 195,000 and 165,000); and Ab AJ2 (Mrs 170,000, 140,000, 140,000, and 28,000).

Animals↗
PubMed1981

The distribution of Helix pomatia lectin receptors on mouse lymphoid cells and other tissues.

The distribution of receptors for the Helix pomatia lectin on mouse lymphoid cells and other tissues was investigated. Using a sensitive rosetting assay combined with immunofluorescence, lectin receptors were found on the membrane of approximately 90% of peripheral T lymphocytes, 75% of thymocytes, 30% of bone marrow cells, 20% of nude spleen cells, 15-50% of peritoneal exudate macrophages, and a subpopulation of peritoneal exudate mast cells. The Thy-1-positive nude spleen cells were predominantly Helix lectin receptor-negative. Approximately 5% of B lymphocytes were weakly positive, and neutrophils were negative. Receptors were present also on a subpopulation of cells of a fibroblast cell line and in acetone powder from the liver and, at a lower level, from the kidney and brain. Membrane receptors on all cell types were partially detectable without neuraminidase treatment of the cells. Two methods of fractionating Helix lextin-positive cells were employed, which gave significantly different results. By rosetting and depletion using density fractionation, T cell mitogen responses were abolished, while B cell mitogen responses, T cell cytotoxicity, and natural killer cytotoxicity were only slightly affected, if at all, Helix lectin-agarose column fractionation seemed more sensitive, in that essentially all natural kill cells bound to the column, as well as considerable number of B lymphocytes. Cytotoxic T cells were heterogeneous; roughly half were not bound, but the remainder were bound and eluted.

Animals↗
PubMed1979

Identification and separation of Thy-1 positive mouse spleen cells active in natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

The expression of the Thy-1 antigen on mouse spleen cells responsible for NK activity and ADCC was investigated by using a monoclonal IgM anti-Thy-1.2 antibody. Both C-mediated cytotoxicity and the fluorescence-activated cell sorter were used to fractionate cells. The effector cells were found to be heterogeneous in their expression of Thy-1. Effector cells from nude BALB/c mice were predominantly Thy-1 positive; some of the NK cells in CBA spleens appeared to be Thy-1 positive, but at least one-third of the lytic activity was due to Thy-1 negative cells. The effects of treatments on NK cytotoxicity and ADCC were very similar, supporting the hypothesis that the same cells mediate both activities.

Animals↗