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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 181 records · Page 10Linked to original sources
PubMed1987

Interactions between growth factor receptors and corresponding monoclonal antibodies in human tumors.

Monoclonal antibodies (MAbs) to the human epidermal growth factor (EGF) receptor, the type I insulin-like growth factor (IGF) receptor, and the nerve growth factor (NGF) receptor were used to study the growth regulation of malignant cells. Anti-EGF receptor MAb 425 inhibited the growth of A 431 squamous carcinoma cells which express high numbers of EGF receptors on their surfaces. Growth inhibition induced by MAb 425 was accompanied by alterations of the cell-cycle distribution of these cells, indicating the ability of a monoclonal antibody to act as a biologically active ligand. Growth stimulation of melanoma cells by EGF was unrelated to EGF receptor expression on the cell surface. Insulin- and IGF-I-induced growth stimulation of melanoma cells was inhibited by MAb alpha IR-3 which reacts with the type I IGF receptor. This result indicates that the type I IGF receptor mediated growth stimulation not only by IGF-I but also by insulin. Normal melanocytes and cells of all stages of tumor progression expressed in tissue culture the receptor for NGF, but no effect on the growth of these cells has been observed.

Antibodies, Monoclonal↗
PubMed1987

Mechanisms of rabies virus neutralization by glycoprotein-specific monoclonal antibodies.

Incubation of radiolabeled rabies virus with neutralizing monoclonal antibodies (MAbs) resulted in complete neutralization of the virus but only partial inhibition of virus binding to, and internalization by, BHK cells. Several of the neutralizing MAbs were capable of preventing infection after virus adsorption to cells; up to 30% of the bound virus was released when cells containing adsorbed virus were incubated with these MAbs at 4 degrees, indicating that the release of bound virus accounts only in part for the neutralization of adsorbed virus. To study the mechanism of neutralization of cell-bound virus, temperature shift experiments were carried out to follow the fate of neutralized cell-adsorbed virus at 37 degrees. Treatment of infected cells with each of the tested neutralizing MAbs had no effect on virus uptake at 37 degrees and the MAbs were endocytosed together with the virus; however, the ability of some of the MAbs to neutralize cell-adsorbed rabies virus correlated with the fusion inhibition activity of these MAbs. We hypothesize from these data that these MAbs neutralize rabies virus by inhibiting the intraendosomal acid-catalyzed fusion step that leads to virus uncoating.

Adsorption↗
PubMed1987

Localization and immunological characterization of antigenic domains of the rabies virus internal N and NS proteins.

To locate epitopes on internal antigens of rabies virus, purified N and NS proteins of the nucleocapsid were cleaved at methionine, tryptophan or glutamic acid residues, transferred to nitrocellulose and immunostained using monoclonal antibodies (MAbs) specific for N and NS proteins, respectively. Five MAb-positive fragments of N protein and one fragment of NS protein were located after NH2-terminal amino acid sequence analysis within the deduced amino acid sequences of N and NS proteins. Antigenic analysis of synthetic overlapping peptides corresponding to the amino acid sequences of these fragments localized two major antigenic sites of N protein and one antigenic site of NS protein. Like the N- and NS-specific MAbs, anti-peptide antisera produced against the different synthetic antigens either reacted in a type-common fashion with all rabies virus strains, or in a type-specific manner with a restricted number of strains. The synthetic peptides corresponding to the three antigenic regions of the N and NS proteins also stimulated proliferation of human T lymphocytes derived from vaccinees who received inactivated rabies virus vaccine. This suggested that the antigenic regions of N and NS proteins are recognized by both B and T cells.

Amino Acid Sequence↗
PubMed1987

Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A.

We have cloned the genomic DNA fragments encoding the heavy and light chain variable regions of monoclonal antibody 17-1A, and we have inserted them into mammalian expression vectors containing genomic DNA segments encoding human gamma 3 and kappa constant regions. The transfer of these expression vectors containing mouse-human chimeric immunoglobulin genes into Sp2/0 mouse myeloma cells resulted in the production of functional IgG that retained the specific binding to the surface antigen 17-1A expressed on colorectal carcinoma cells.

Amino Acid Sequence↗
PubMed1987

Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies.

The detection of early micrometastasis or disseminated single tumor cells poses a problem for conventional diagnosis procedures. Using a panel of monoclonal antibodies against cytokeratin and the 17-1A epithelial antigen we identified immunocytochemically tumor cells in bone marrow of patients with breast cancer (n = 155) and colorectal cancer (n = 57) at the time of surgery of the primary tumor. Monoclonal antibody CK2, recognizing the human cytokeratin component 18 in simple epithelia, appeared to be the most suitable reagent because of its negative reaction with bone marrow samples of the noncarcinoma patients (n = 75). Its specificity was further demonstrated in a double-marker staining procedure using an anti-leukocyte common antigen monoclonal antibody (T200) as counterstain. A comparative analysis showed that immunocytology was clearly superior to conventional cytology (n = 212) and histology (n = 39). In 9.5-20.5% of patients without distant metastasis, tumor cells could be detected in bone marrow. We found a significant correlation between tumor cells in bone marrow and conventional risk factors, such as distant metastasis or lymph node involvement. In a first approach toward immunotherapy we demonstrated in 3 patients that infused monoclonal antibody 17-1A can label single tumor cells in bone marrow in vivo. We then used this approach to follow up 7 patients undergoing 17-1A therapy in an adjuvant clinical trial.

Antibodies, Monoclonal↗
PubMed1987

Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein.

We have studied the ability of rabies virus ribonucleoprotein (RNP) to induce a protective immune response in animals against lethal challenge with rabies and rabies-related lyssa viruses. Liposomes containing either RNP or the glycoprotein (G protein) of a variant virus with multiple alterations in the G antigenic structure conferred no or poor protection, respectively, against lethal intracerebral challenge with rabies virus. By contrast, liposomes containing RNP and the variant G protein induced a good protective response, comparable to that achieved with inactivated virus vaccine against intracerebral challenge. Moreover, mice or raccoons immunized with RNP alone resisted lethal peripheral challenge with homologous or heterologous virus strains. These results indicate that the RNP of rabies virus plays a crucial role in induction of protective immunity.

Animals↗
PubMed1987

HTLV-I infection of cerebrospinal fluid T cells from patients with chronic neurologic disease.

Antibodies reacting with HTLV-I, the etiologic agent of acute T cell leukemia/lymphoma and a transforming agent for T4-positive lymphocytes in vitro, have recently been described in sera of patients with chronic neurologic disease in the absence of lymphoproliferative disorders. The largest number of such cases was described in Japan and in the Caribbean and parts of South America. We report here two cases of patients with chronic neurologic disease whose cerebrospinal fluid (CSF)-derived T cells contain HTLV-I specific RNA sequences and antigens and are expressing retroviral particles. Only one of these patients has demonstrable antibody to HTLV-I in serum or CSF.

Adult↗
PubMed1987

A mucin containing the X, Y, and H type 2 carbohydrate determinants is shed by carcinoma cells.

Monoclonal antibody BR 15-6A directed to the Y carbohydrate determinant (Fuc alpha 1----2Gal beta 1----4GlcNAc(3----1Fuc) beta 1----3Gal beta 1----4Glc beta 1----1Cer) reacted with the cell surface and conditioned media of colorectal and breast carcinoma cell lines. Double determinant immunoassays using BR 15-6A as detector antibody showed that the Y determinant is part of a high molecular weight mucin that coexpressed other carbohydrate antigens based on a type 2 chain (X, H type 2). Type 1 chain carbohydrates such as sialylated Lewisa, Lewisa and Lewisb blood group antigens were predominantly expressed on a separate mucin molecule as determined by double-determinant immunoassays with other anticarbohydrate monoclonal antibodies. The X, Y, and H type 2-bearing mucin was present in conditioned media of the majority of colorectal carcinoma cell lines and in all three breast cancer cell lines tested. Thus, monoclonal antibodies against X, Y, and H type 2 determinants are potentially useful in the serodiagnosis of gastrointestinal and breast cancer.

Antibodies, Monoclonal↗
PubMed1987

Antigenic variation in rabies and rabies-related viruses: cross-protection independent of glycoprotein-mediated virus-neutralizing antibody.

Immunization experiments with vaccines prepared from the PM and ERA strains of rabies virus demonstrated that in mice, only ERA vaccine primes for an anamnestic response to the rabies-related strain Duvenhage (DUV6); in rabbits, both ERA and PM vaccines induced immunologic memory to DUV6 virus. In mice, ERA vaccine, but not an equal concentration of PM vaccine, conferred protection against a lethal challenge infection with DUV6 virus. This result indicated that the protective activity correlated with the vaccine's ability to induce immunologic memory. A vaccine prepared from a sequentially selected, neutralization-resistant, multiple-variant virus conferred protection against challenge with the parental strain, a result indicating that antigenic variation of the glycoprotein may not be the sole factor in determining the relative efficacy of rabies prophylaxis. We found no correlation between titers of neutralizing antibody and mortality rates in mice immunized with purified glycoprotein from these viruses.

Animals↗
PubMed1987

Neoexpression of ABH and Lewis blood group antigens in human hepatocellular carcinomas.

Expression of blood group ABH, Lewis, and sialylated-Lea antigens in human hepatocellular carcinomas and the adjacent nontumorous liver tissues was investigated with the use of seven monoclonal antibodies against these carbohydrate determinants. Chromatogram antibody-binding assay and solid-phase enzyme immunoassay of the upper-phase neutral glycolipids revealed the tumor-associated expression of blood group A-active glycolipids incompatible with blood-type status of the patients, a blood group A-active glycolipid with mobility on thin-layer chromatography between the known 6- and 8-sugar blood group A-active glycolipids in human erythrocytes, blood group H-active glycolipids, and blocked synthesis of Lea-active glycolipids with or without concomitant accumulation of Leb-active glycolipids. Immunohistochemical analysis of the fixed tissues with the use of an avidin-biotin-peroxidase complex method revealed blood group antigens in biliary epithelial cells but not in parenchymal liver cells. However, hepatocellular carcinoma cells in some cases expressed H and Leb antigens. Although only type 1 chain H antigen was detected in biliary epithelial cells, both type 1 and type 2 chain H antigens were found in hepatocellular carcinoma cells.

ABO Blood-Group System↗
PubMed1987

Purification and amino terminal sequencing of human melanoma nerve growth factor receptor.

The nerve growth factor (NGF) receptor, solubilized with Triton X-100 detergent, has been purified from human melanoma cell line A875. Purification to near-homogeneity was achieved by chromatography on wheat germ agglutinin-agarose, followed by immunoaffinity chromatography on Sepharose columns coupled with anti-NGF receptor monoclonal antibody (MAb). The purified receptor, a 75,000-dalton protein, retains the capacity to bind NGF as well as anti-receptor MAbs. Final purification was achieved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sequence of amino acid residues at the amino terminus has been determined. Possible sequence homology between the NGF receptor and several other proteins is discussed. Using the purified receptor as immunogen, new MAbs to the NGF receptor have been produced. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of dorsal root ganglia from monkeys.

Amino Acid Sequence↗
PubMed1987

Biology of tumor progression in human melanocytes.

Tumor progression in the human melanocyte system can be delineated into 6 sequential stages. The first three steps represent nonmalignant melanocyte lesions from focal proliferations of structurally normal melanocytes to lesions with architectural and cytologic atypia. Primary melanoma may be divided into radial growth phase without competence for metastasis and vertical growth phase with metastatic competence. Melanocytes isolated from normal skin, nonmalignant pigmented lesions, and melanomas and maintained in culture have properties that are characteristic for each stage of tumor progression. Cytogenetic studies revealed nonrandom chromosomal abnormalities of advanced melanomas involving chromosomes 1, 6, and 7. Recent progress in tissue culture techniques has allowed studies of growth regulation of normal and malignant cells. Six growth factor receptor-growth factor systems seem to be of biologic significance in the melanocyte system: EGF, NGF, FGF, PDGF, insulin, and beta-TGF. Monoclonal antibodies have characterized a large number of antigens on melanocytes of the various stages of tumor progression, making melanoma one of the most widely studied human tumor systems.

Antigens, Neoplasm↗
PubMed1986

GD2 ganglioside biosynthesis is a distinct biochemical event in human melanoma tumor progression.

Gangliosides from cell cultures established from melanocytic lesions, representing different stages of melanoma tumor progression, were analyzed by chemical and immunological means on thin-layer chromatograms. The GD2 ganglioside and N-acetylgalactosaminyl transferase, which catalyzes the biosynthesis of GD2 from its precursor GD3, were detected in cultures established from advanced primary and metastatic melanomas, but not in cultures of normal melanocytes. Immunohistochemical studies on tissue sections from all progression stages confirmed GD2 expression only in these advanced lesions. A distinct biochemical event thus coincides with the onset of faster growth and acquisition of metastatic competence in human melanoma tumor progression.

Autoradiography↗
PubMed1986

Identification of NGF receptor in chromatin of melanoma cells using monoclonal antibody to cell surface NGF receptor.

A 230 KDa species of Nerve Growth Factor (NGF) receptor was immunoprecipitated from EcoRI-digested chromatin of melanoma cells using a monoclonal antibody to the 75 KDa cell surface NGF receptor. The chromatin NGF receptor was shown to exist tightly bound to DNase II-sensitive sequences which, upon growth factor binding, became resistant to DNase II digestion.

Antibodies, Monoclonal↗