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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 325 records · Page 18Linked to original sources

Central nervous system infection and immune response in mice inoculated into the lip with herpes simplex virus type 1.

Virus may be recovered from various areas of the central nervous system (CNS) of mice for as long as 11 days after inoculation of herpes simplex virus type 1 (HSV-1) into the lip. The probability of isolation from any particular region of the CNS seems to be a function of the distance of that area from the root-entry zone of the trigeminal nerve. It is also mouse strain-dependent, with much more extensive evidence of brain infection being found in BALB/c and C3H rather than C57BL/6 mice, in which it is limited to the pons. The virus could not be isolated from the CNS of BALB/c mice after 10 days, though HSV-1 is readily recovered from the trigeminal ganglia at least through day 38. Significant concentrations of HSV-1-specific immunoglobulin (Ig) were demonstrated consistently in cerebrospinal fluid (CSF) from day 12 after exposure to virus. The persistence of relatively high concentrations of IgM in the CSF indicates that much of this antibody may be synthesized locally in the brain.

Animals↗

DR antigens on melanoma cells: analysis with monoclonal antibodies.

Two monoclonal antibodies (691-13-17 and 37-7) can precipitate DR antigens from radioiodinated, detergent solubilized melanoma cells. However, after complete depletion of lysates with one antibody (691-13-17) alpha-like chains can be still be precipitated from some melanoma cells by the other antibody (37-7). Antibody 37-7 also precipitates an additional distinct antigen from SK-MEL 37 but not from any five other melanoma cell lines.

Animals↗

IgG2a monoclonal antibodies inhibit human tumor growth through interaction with effector cells.

Monoclonal antibodies of IgG2a isotype specifically inhibited growth of human tumors in nude mice. Twenty-three monoclonal antibodies of other isotypes showed no tumoricidal reactivity. Complement depletion of nude mice had no effect on tumor suppression by monoclonal antibody. The role of T and killer cells as mediators of the monoclonal antibody effect in nude mice was virtually excluded. On the other hand, macrophages were strongly incriminated as effector cells because silica treatment of nude mice abolished the tumoricidal effect of monoclonal antibody. IgG2a monoclonal antibody-dependent macrophage-mediated cytotoxicity assays with human tumor cells in culture resulted in specific lysis of tumor cells.

Animals↗

Antigen-specific human T-cell hybridomas with helper activity.

Human T cell hybridomas were produced by fusing the hypoxanthine phosphoribosyltransferase-deficient line of the human T cell lymphoma Jurkat with a continuous line of normal human T cells specific for tetanus toxoid (TeT). The hybridomas were selected for their ability to produce interleukin 2 after exposure to TeT on semiautologous monocytes and for their ability to bind to TeT-pulsed semiautologous monocytes. These antigen-specific T hybridomas demonstrated potent helper activity for semiautologous B cells as determined by the production of high levels of anti-TeT antibody in vitro.

Antibody Formation↗

Expression of DR antigens in freshly frozen human tumors.

DR antigens are thought to function as differentiation antigens and to restrict immune recognition between T cells and B cells, monocyte/macrophages, Langerhan's cells, and endothelial cells. These antigens are commonly found on tissue culture lines from metastatic melanomas and tumors of lymphocyte derivation but are notably uncommon on cell lines from other malignancies. Using frozen tissue sections, a monoclonal antibody (WI 691-13-17) known to detect an epitope common to all DR alloantigens on the beta (light) chain of DR antigens, and a two-step indirect immunoperoxidase technique, DR antigens were found on all metastatic lesions tested and on many primary tumors and their histogenetic precursors. The technique of using monoclonal antibodies in indirect immunoperoxidase staining of freshly frozen tissue allows individual cells to be assessed for antigen expression and presumably more accurately reflects in vivo antigen expression than results obtained from cells selected by tissue culture methods.

Antibodies, Monoclonal↗

Human anti-tetanus toxoid monoclonal antibody secreted by EBV-transformed human B cells fused with murine myeloma.

An Epstein-Barr virus (EBV)-transformed human B cell line (B6) producing anti-tetanus toxoid (TT) antibody was fused with a nonimmunoglobulin (Ig)-producing murine myeloma and selected in hypoxanthine-aminopterin-thymidine (HAT) medium containing 10(-5) M ouabain. Surviving cells were cloned by limiting dilution and confirmed as hybrids by karyotype analysis and G-11 staining. Hybridomas were stable and secreted 10-fold more anti-TT antibody (IgM kappa) than the human parental cell line. In addition, the hybridomas exhibited a markedly reduced growth requirement for serum (1% fetal calf serum). Since EBV can be used to expand rare antigen-specific B cells in the human, the technique described here may be at present the method of choice for producing human monoclonal antibodies.

Animals↗

Comparative study of the binding characteristics of monoclonal antimelanoma antibodies.

The binding specificities of monoclonal antibodies against human cutaneous malignant melanoma were analyzed using radioimmunoassay (RIA), mixed hemadsorption assay (MHA), and peroxidase-antiperoxidase assay on a variety of malignant and nonmalignant cells. Twenty-four of the 30 monoclonal antibodies bound to the majority of melanoma cell lines tested, and only two antibodies did not bind to any of the melanoma lines. Three antibodies bound to melanoma lines only, 13 antibodies reacted also with fetal cells, 21 antibodies bound to at least one carcinoma cell line and nine antibodies reacted with one or more cell lines of leukemic or lymphoid origin. The antibodies could be divided into seven groups based on their binding characteristics. These groups had been established by a panel of monoclonal antimelanoma antibodies produced and characterized at The Wistar Institute.

Antibodies, Monoclonal↗

Identification and isolation of melanoma-associated antigens with monoclonal antibodies.

The monoclonal antibodies distributed at the first Workshop on Monoclonal Antibodies to Melanoma have been tested by immunoprecipitation, and one group of antigens (90 kd) has been found to be identical by sequential immunoprecipitation. These results are in good agreement with those from other laboratories. In addition, antigens from a new group of hybridomas, generated since the first Workshop, were studied. Some of these antigens are unique and others are duplicates of the original set. Finally, a melanoma-associated antigen (260 kd) was purified by immunoaffinity chromatography.

Antibodies, Monoclonal↗

Use of monoclonal antibodies in detection of melanoma-associated antigens in intact human tumors.

The use of antimelanoma monoclonal antibodies on tissue sections using a two-step indirect immunoperoxidase technique is reported. Antibodies 691-13-17 and 691-I5-Nu4B reacted with dysplastic nevus cells and all melanomas tested, but not with normal skin melanocytes, intradermal nevi, or lentigines. Antibody 691-13-17, directed against DR antigen, reacted also with Langerhan's cells, macrophages, and a subpopulation of lymphocytes. Antibody 691-I5-Nu4B reacted only with melanomas. The technique allows analysis of the expression of antigens by tumor cells in situ.

Adult↗

Gastrointestinal cancer-associated antigen in immunoperoxidase assay.

A monosialoganglioside antigen of gastrointestinal adenocarcinomas defined by murine monoclonal antibody was demonstrated by immunoperoxidase (IP) assay in fixed paraffin-embedded tumors in 59% of colonic adenocarcinomas, 86% of pancreatic adenocarcinomas, and 89% of all gastric adenocarcinomas. In all patients with detectable levels of antigen in circulation, the resected tumors also expressed the antigen in IP assay. Six of eight individuals with no detectable levels of antigen in their serum samples expressed the antigen in the tumor tissue. Removal of the sialic acid residue of the antigen abolished the IP reaction. The successful use of the IP assay on fixed tissue to demonstrate the specific sites of gastrointestinal cancer antigen localization in human tumors and normal tissues provides an important tool for the study of developing neoplasia.

Adenocarcinoma↗

Monoclonal antibody-defined human lung cell surface protein antigens.

Monoclonal antibodies were used to define four distinct antigens present on the surface of human lung tumors. Immunoprecipitation of the four antigens by monoclonal antibodies and sodium dodecyl sulfate:polyacrylamide gel electrophoresis reveals that they have distinct complex structures. Different patterns of expression of these antigens on cells of other than lung tumor origin were detected by the same panel of monoclonal antibodies.

Antibodies, Monoclonal↗

Monoclonal antibodies directed against the human Leb blood group antigen.

Four monoclonal antibodies produced by hybridomas obtained from a mouse immunized with a human adenocarcinoma cell line SW1116 (Koprowski, H., Steplewski, Z., Mitchell, K., Herlyn, M., Herlyn, D., and Fuhrer, P. (1979) Somatic Cell Genet. 5, 957-972) are directed against the Leb antigen of the human Lewis blood group system. Their specificities were established by binding studies using purified Leb-active ceramide hexasaccharide and by hapten inhibition studies involving oligosaccharides obtained from human milk.

Antibodies, Monoclonal↗

Monoclonal anticolon carcinoma antibodies in complement-dependent cytotoxicity.

Hybridoma-derived monoclonal anticolon carcinoma (ACC) antibodies mediated specific complement-dependent cytotoxicity (CDC) against human colon carcinoma cells either grown in culture or obtained directly from patients. These ACC antibodies did not lyse normal colonic mucosa or other normal and malignant human cells. Absorption of these antibodies to cells of established colon carcinoma cell lines totally eliminated their specific lytic capacity. ACC antibodies were able to bind in vivo to colon carcinoma cells grown in nude mice but did not bind to lung or kidney cells from tumor-bearing animals. These monoclonal antibodies did not, however, inhibit the growth of colon carcinoma tumor cells in nude mice.

Absorption↗

Specific antigen in serum of patients with colon carcinoma.

The binding of monoclonal antibody specific for colon carcinoma was inhibited by serum from patients with adenocarcinoma of the colon but not by serum from patients with other bowel diseases or from healthy volunteers. Of other malignancies studied, serum from two patients with gastric carcinoma and two patients with pancreatic carcinoma also inhibited the specific binding of monoclonal antibody. The levels of carcinoembryonic antigen in these serum samples were not correlated with their levels of binding inhibition. Such monoclonal antibodies may prove useful for the detection of colorectal carcinoma.

Adenocarcinoma↗

A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma.

The antigen of a monoclonal antibody that is specific for cells of human carcinoma of the colon is a monosialoganglioside as determined by the direct binding of antibody to thin-layer chromatograms of total lipid extracts of tissues. Binding of antibody to chromatograms is detected by autoradiography after the application of iodine-125-labeled F(ab')2 of rabbit immunoglobulin G antibodies to mouse immunoglobulins.

Adenocarcinoma↗

Epstein-Barr virus in nontumorigenic and tumorigenic nasopharyngeal carcinoma (NPC) somatic cell hybrids.

Somatic cell hybrids between mouse fibroblasts and human cells derived from nasopharyngeal carcinoma (NPC) biopsies or NPC tumors propagated in nude mice were examined for the expression of the Epstein-Barr nuclear antigen (EBNA), retention of Epstein-Barr viral (EBV) DNA, and tumorigenicity in nude mice. In all hybrids the expression of EBNA correlated with the detection of EBV-DNA. After more than 2 years in culture, the hybrids examined retained similar amounts of EBV-DNA when compared to previously published data. Retention of EBV-DNA did not correlate with the presence of any particular human chromosome. Use of either rodent cell lines, clone 1D or IT-22, did not affect the retention nor loss of EBV-DNA. For tumorigenicity studies, NPC cells were fused with IT-22 cells and injected into nude mice. Tumor formation did not depend on the presence or absence of EBNA and detectable EBV-DNA sequences; tumorigenicity in these studies could not be correlated with the presence of any particular human chromosome or the origin of the NPC biopsy.

Animals↗