Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 271 records · Page 15Linked to original sources

PubMed1984

A fetal glycolipid expressed on adenocarcinomas of the colon.

Reactivity of neuraminidase-treated colorectal carcinoma cells with antibodies that detect the X-carbohydrate structure was greater than the reactivity of untreated cells. The same results were obtained with glycolipid extracts of meconium, a colorectal carcinoma cell line, three freshly excised human adenocarcinomas, and normal bronchial mucosa. The glycolipid was either not expressed or expressed in smaller quantities on the corresponding normal colon tissue. Further study showed that the major sialo-X glycolipid has six sugars including a single sialic acid which blocks X-antigenicity. These glycolipids were further analyzed by ion-exchange high-pressure liquid chromatography and thin-layer chromatography. These monosialo-X glycolipid antigens might serve as potential tumor markers.

Adenocarcinoma↗

PubMed1984

Extraction of circulating gastrointestinal cancer antigen using solid-phase immunoadsorption system of monoclonal antibody-coupled membrane.

An immunoadsorption system of monoclonal antibody immobilized on a polyolefin alloy fiber is described for extraction of serum gastrointestinal cancer antigen (GICA). Continuous circulation or single passage of plasma from gastrointestinal cancer patients through this antibody-fiber matrix resulted in 90% depletion of circulating GICA in 2 h using 0.6 mg immobilized antibody, and 90% depletion in 5 min using 8 mg antibody. Continual circulation resulted in total GICA removal in both cases. Desorption of antibody or of antibody-containing complexes was minimal. This methodology provides a selective and convenient means of removing any targeted substance by monoclonal antibody from the serum, and thus overcomes many of the shortcomings associated with conventional plasmapheresis.

Animals↗

PubMed1984

Increased levels of circulating HLA-DR antigen in sera of patients with acute lymphoblastoid leukemia.

Monoclonal antibodies that define HLA-DR antigen bind to a variety of human tumors, such as Burkitt lymphoma and melanoma cells grown in vitro and with the spent medium of these cultures. Two radioimmunoassays have been developed to detect HLA-DR antigen circulating in human sera. The inhibition assay is based on the inhibition of binding of monoclonal antibodies against HLA-DR to the target preparation; the double-determinant assay traces antigen bound by a solid-phase monoclonal antibody by the use of a second 125I-labeled antibody. Twenty-six of 39 sera from patients with acute lymphoblastoid leukemia, 2 of 29 sera from patients with acute myeloid leukemia, and 5 of 31 sera from patients with advanced metastatic melanoma showed increased levels of HLA-DR antigen, whereas none of 28 sera from patients with other malignancies had increased levels of HLA-DR antigen, and only 2 of 155 sera from healthy donors bound monoclonal antibodies to HLA-DR at detectable levels. The detection of circulating HLA-DR antigen in sera of cancer patients may be useful in monitoring patients with certain malignancies.

Antibodies, Monoclonal↗

PubMed1984

Cytogenetics of human malignant melanoma and premalignant lesions.

Chromosome studies were done on direct preparations, early passage cultures, and/or cell lines derived from melanocytic lesions of 17 patients. There were 5 nevi (3 dysplastic); 1 early primary melanoma (radial growth phase); 1 advanced primary melanoma (vertical growth phase) with multiple metastases; and 10 metastatic lesions. The 5 nevi had normal karyotypes, while each of the tumors had a predominantly abnormal karyotype. The early melanoma was pseudodiploid, including a 6p;22 translocation. Ten of the 11 advanced melanomas had one or more aberrations involving chromosome #1, with 9 having deletions or translocations of lp that involved the proximal segment 1p12----1p22 9 times in 8 lesions. Six advanced tumors had additional material involving 7q, including extra #7s (4 cases) and 7q+ (2 cases). Nine melanomas, including the early tumor, had alterations in chromosome #6. Three had additional copies of 6p (as iso6p or t6p); the others showed no consistent pattern. In one advanced tumor, the primary lesion and 5 metastases (removed seriatim over an 18-month period) had nearly identical karyotypes, indicating the clonal nature of the neoplasm. The nonrandom cytogenetic changes suggest that genes important in melanoma carcinogenesis are located on the proximal portion of 1p, on 7q, and on chromosome #6. More data on early lesions are needed to identify the relation of these various cytogenetic changes to the different stages of malignant melanoma development.

Cell Line↗

PubMed1984

Human anti-idiotype antibodies in cancer patients: Is the modulation of the immune response beneficial for the patient?

Inoculation of human subjects with mouse monoclonal antibody results in the production of anti-idiotype antibody that reacts with the binding site of the monoclonal antibody. This reaction is hapten-inhibited, suggesting that an internal image of the antigen is produced by the anti-idiotype response. The anti-idiotype antibody isolated from sera of three patients showed significant crossreactivity. Patients who developed the anti-idiotype antibody improved clinically and had long remission from their disease. The possible presence of the internal image of cancer antigen on the human immunoglobulin molecule may change the conditions under which the immune system reacts to the tumor antigen and may open new approaches to the control of tumor growth.

Adenocarcinoma↗

PubMed1984

Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis.

Monoclonal antibodies of the IgG2a isotype specifically inhibit the growth of human tumors in nude mice; tumors in mice given no antibody, an antibody of the IgG2a isotype that does bind to the tumor cells, or an antibody of the IgG2b isotype grow progressively. In the present work it is demonstrated that tumors of mice given the IgG2a antibody are essentially masses of necrosis, while tumors from the control mice are sheets of healthy tumor cells. Tumors of the treated mice, in comparison to controls, contain an increased number of macrophages, and these macrophages are activated for a distinct form of cytolysis dependent on antibodies of the IgG2a isotype. The data suggest that changes in the number and function of intratumoral macrophages are a major component of tumor destruction mediated by IgG2a antibodies.

Animals↗

PubMed1984

Identification and isolation of Lewis blood group antigens from human saliva using monoclonal antibodies.

Solid-phase radioimmunoassay, polyacrylamide gel electrophoresis and thin-layer chromatography were used to compare, identify, and characterize the Lewis antigens from human salivas, using monoclonal antibodies directed to the Lea and Leb determinants. Sialylated Lea glycolipid was detected in saliva from individuals with Le(a+ b+) and Le(a+ b-) phenotypes. Immunoaffinity chromatography of the saliva from individuals with different phenotypes revealed a glycoprotein of molecular weight greater than 200 kD bearing the Lewis antigenic determinants.

Antibodies, Monoclonal↗

PubMed1984

Characterization of saturable binding sites for rabies virus.

A specific, saturable receptor for rabies virus was analyzed on cultured cells of neural or non-neural origin. Viral attachment kinetics were enhanced by DEAE-dextran, an effect which in turn enhanced the apparent infectivity of the virus inoculum. Under optimized conditions, the attachment of metabolically labeled ERA strain rabies virus obeyed the laws of mass action, whereby the amount of virus bound to cells varied proportionally with the concentration of cells or virus. Attachment was sensitive to changes of temperature and pH, did not require divalent cations such as Mg2+ or Ca2+, and occurred despite prior treatment of cells with proteolytic or sialic acid-specific enzymes. Saturation of the cell surface with rabies virus could be accomplished with 3 X 10(3) to 15 X 10(3) attached virions per cell. Competition for the rabies receptor occurred with rabies nonpathogenic variant virus, RV194 -2, and vesicular stomatitis virus. Reovirus type 3, another neurotropic virus, failed to inhibit rabies virus binding, and West Nile virus only slightly inhibited rabies virus binding, suggesting independent cellular receptors were recognized by these viruses. Isolated rabies virus glycoprotein failed to compete in an equivalent manner. However, solubilization of BHK-21 cells with octylglucoside yielded a chloroform-methanol-soluble extract which blocked rabies virus attachment. The binding inhibition activity of this extract was resistant to proteases but could be destroyed by phospholipases and neuraminidase, suggesting a phospholipid or glycolipid component at the receptor site. These data provide evidence for a rhabdovirus-common mechanism for cellular attachment to cells in culture.

Animals↗

PubMed1984

Detection of a circulating gastrointestinal cancer antigen in sera of patients with gastrointestinal malignancies by a double determinant immunoassay with monoclonal antibodies against human blood group determinants.

Monoclonal antibodies (MoAbs) produced against determinants A and B of the human ABO blood group system and against the Lea and Leb determinants of the Lewis (Le) blood group system detected these determinants on molecules released by cultured cells of human colorectal, gastric and/or pancreatic carcinoma (Ca) but not by a variety of other cells maintained in culture. Circulating Le antigen could be demonstrated in sera of patients by inhibiting the binding of MoAbs to a target preparation. A double determinant radioimmunoassay (DDIA) was then developed to detect the association of blood group determinants with a previously defined gastrointestinal cancer antigen (GICA). The DDIA with the anti-blood group and anti-GICA antibody was in some cases more sensitive in detecting GICA in sera than using the anti-GICA MoAb alone. Of 55 sera from patients with primary and early recurrent colorectal carcinoma (CRC), 10 (18%) were scored positive in the DDIA using only anti-GICA MoAb. When MoAb binding to a determinant on Leb and on H, type I, was used as first antibody in DDIA followed by anti-GICA MoAb 11 additional sera were reactive, increasing the percentage of positive sera to 38. Using the same combinations of MoAbs, the sensitivity of detection of GICA was only slightly improved from 63 to 66% in sera of patients with advanced CRC. The number of false positive sera from patients with non-malignant gastrointestinal diseases or from healthy donors remained at low levels when anti-blood group determinant antibodies were used together with anti-GICA MoAb. The results indicate that DDIAs with MoAbs against different blood group determinants and tumour associated antigens can improve the detection of circulating antigens in patients with early stage cancer.

ABO Blood-Group System↗

PubMed1984

T cell responses to cleaved rabies virus glycoprotein and to synthetic peptides.

The antigenic structure of the rabies virus glycoprotein has been studied. A limited number of fragments were obtained by cyanogen bromide (CNBr) cleavage of viral glycoprotein, and eight large peptides were isolated by using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. These were tested for their capacity to stimulate the proliferation of nylon wool-purified T cells obtained from spleens of rabies-immune A/J mice. Three peptides (Cr1, Cr2 plus Cr2A, and Cr3) stimulated antigen-specific proliferation, indicating that at least three T cell determinants of the native molecule are sequential or continuous in nature. Stimulation was also obtained with 27-residue and 13-residue synthetic peptides (designated R21 and R20, respectively) that included sequences towards the carboxy terminal end of Cr1, but not with synthetic peptides that included sequences of Cr2 and Cr3 (which are both glycosylated in virus-derived material). The intact viral glycoprotein and synthetic peptide R21 stimulated T lymphocytes with surface characteristics of helper cells, and induced the production of interleukin 2 by these lymphocytes. Synthetic peptides R20 and R21 also stimulated a minor population of Lyt-2-positive cells, which were not yet identified as either suppressor or cytotoxic T lymphocytes.

Animals↗

PubMed1984

Characterization of gastrointestinal tumor-associated carcinoembryonic antigen-related antigens defined by monoclonal antibodies.

Four major carcinoembryonic antigen-related glycopeptides (Mr 180,000, 160,000, 50,000, and 40,000) were detected in SW948 colon carcinoma cells and in colon adenocarcinoma tissue using a monoclonal antibody (C(4)20-32) generated by immunizing mice with SW1222 human colon carcinoma cells. Only the Mr 50,000 polypeptide was immunoprecipitated from normal colon mucosa by this antibody. Binding studies using other monoclonal antibodies and lectins indicated the different epitopes and carbohydrate attachment sites on each of the four polypeptides. Only monoclonal antibody C(4)20-32 recognized a common determinant on all four polypeptides which was revealed by its reactivity with each affinity-purified component.

Adenocarcinoma↗

PubMed1984

Immunoscintigraphy of colon carcinoma.

Two I-131 labeled monoclonal antibodies that react specifically with human gastrointestinal cancers in cell cultures were administered to 90 cancer patients for the scintigraphic detection of cancer sites. Antibody 17-1A, or its F(ab')2 fragments, accumulated significantly in 27 of 46 (59%) colorectal cancer sites, but not in 21 nonepitheliomatous colon cancers and cancers at other sites. Antibody 19-9, or its F(ab')2 fragments, showed significant accumulation in 19 out of 29 (66%) colorectal cancer sites. In 17 patients, immunoscintigraphy with antibody 19-9 correlated with an immunoperoxidase study with the same antibody on resected tissue specimens. In 12 patients injected with two antibodies (17-1A + 19-9, or anti-CEA + 19-9), ten of 13 colorectal cancer sites were positive.

Adult↗

PubMed1984

Monoclonal antibody localization of Lewis antigens in fixed tissue.

Monoclonal antibodies that bind specifically with Lewisa (Lea) and Lewisb (Leb) antigens were used in an immunoperoxidase assay to characterize Lewis (Le) antigenic profile of a variety of fixed tissues. Representative sections of normal and malignant tissue from the stomach, colon, pancreas, and kidney were examined and compared. Lea antigen was expressed more often in gastric adenocarcinomas (80%) than normal gastric mucosa (40%). In gastric tumors with concomitant expression of Le antigens, larger areas within an individual tumor expressed Lea antigen rather than Leb antigen. Expression of Leb antigen in normal colonic tissue was seen only in the proximal colon and not distal colon; colon carcinomas, on the other hand, expressed Leb antigen (64%) regardless of where the primary arose. Leb antigen was expressed in large pancreatic ducts (three of three) more often than Lea antigen (one of three); exclusive expression of Lea antigen was demonstrated in the proximal convoluted tubules of normal kidney (three of three) and in renal cell carcinomas (six of eight).

Animals↗

PubMed1984

Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma.

Twenty patients with metastasis of gastrointestinal malignancies were treated with an anti-colorectal cancer mouse monoclonal antibody 1083-17-1A of the IgG2a class between December 1980 and January 1983. With two exceptions, all patients received a single injection of monoclonal antibody in a dose range of 15-1,000 mg/patient. No untoward immediate or delayed reaction to the initial injection was observed in any of the patients. Mouse immunoglobulin circulated in the patients' blood for 2-50 days, depending on the dose of monoclonal antibody injected, and was detected in tumor tissue within 1 week of its administration. Eight of nine patients who received doses of 366-1,000 mg monoclonal antibody did not develop anti-mouse antibodies, while eight of nine who received less than 200 mg developed anti-mouse immunoglobulin antibody. Three of this heterogeneous group of patients have no detectable disease now--10, 13, and 22 months since immunotherapy.

Adenocarcinoma↗

PubMed1984

Immunoassay for melanoma-associated proteoglycan in the sera of patients using monoclonal and polyclonal antibodies.

A melanoma-associated proteoglycan antigen is expressed by primary cutaneous and ocular melanomas, metastatic melanomas, nevus cells, some astrocytomas, and fetal fibroblasts, and it is shed into culture supernatant by both melanoma and nevus cells. The antigen is also expressed by tumor cells in vivo. Melanoma and nevus cells, but not normal melanocytes, were specifically stained by the immunoperoxidase procedure. The proteoglycan antigen, purified by immunoaffinity chromatography using a monoclonal antibody that specifically detects this antigen, was used to immunize rabbits. The resulting serum was tested by sequential immunoprecipitation and found to react with the same population of molecules detected by the anti-proteoglycan monoclonal antibodies. Furthermore, the reactivity patterns of the rabbit serum and of the monoclonal antibodies with a variety of tumor and normal cells were the same. Based on the these data, we conclude that the entire proteoglycan molecule is a melanoma-associated antigen. The monoclonal antibodies and immunoglobulin from the rabbit serum were tested in a double determinant immunoassay for the detection of antigen in a total of 339 sera from patients with various diseases. Elevated levels of circulating proteoglycan antigen were found in 76% of patients with a high metastatic melanoma tumor burden compared to 2% of healthy donors. A fraction (22%) of patients with light tumor burden or nonmelanoma neoplastic disease also had elevated levels of circulating proteoglycan antigen. The source of the antigen for the latter patients may be collagenous connective tissue which, as judged by immunoperoxidase staining, expresses the antigen in both normal and transformed tissues.

Antibodies↗

PubMed1984

Induction of mouse IgG2a- and IgG3-dependent cellular cytotoxicity in human monocytic cells (U937) by immune interferon.

The effects of natural and recombinant human gamma-interferon (IFN-gamma) on mouse monoclonal antibody-dependent cellular cytotoxicity (ADCC) mediated by U937 human monocytic-like cells were examined. The efficiency of mouse monoclonal antibody of different isotypes in inducing ADCC was also compared. The number of receptors for the Fc portion of immunoglobulin G (IgG) (FcR) for mouse IgG2a and IgG3 on U937 cells, as detected by IgG antibody-sensitized erythrocyte rosette formation, was significantly enhanced by IFN-gamma. In contrast, FcR for mouse IgG1 and IgG2b were not detected even after IFN-gamma stimulation. U937 cell-mediated ADCC against sheep or ox red blood cell targets was minimal. However, after incubation with human purified IFN-gamma, U937 cells exhibited increased activity in IgG2a- and IgG3-dependent lysis, whereas their activity in IgG1- and IgG2b-dependent lysis was low. ADCC stimulated by IFN-gamma was inhibited by Protein A. When mouse peritoneal exudate cells were used, FcR for all IgG isotypes were easily detected, and all IgG isotypes mediated ADCC. Taken together, these results indicate that IFN-gamma induces U937 cell ADCC with mouse IgG2a and IgG3 partly through augmentation of FcR expression. Recombinant IFN-gamma showed the same effect as natural IFN-gamma. These effects of IFN-gamma were completely abrogated by anti-IFN-gamma serum but not by anti-IFN-alpha or normal rabbit serum. Addition of polymyxin B or lipopolysaccharide did not affect the activity of IFN-gamma.

Animals↗

PubMed1984

Monoclonal antibody localization of A and B isoantigens in normal and malignant fixed human tissues.

The expression of human blood group A and B isoantigens in normal and malignant tissues from stomach, colon, and pancreas was analyzed in an immunoperoxidase assay using monoclonal antibodies specific for these isoantigens. Appropriate isoantigen expression was demonstrated in the normal epithelium from the stomach, pancreas, and proximal but not distal colon of blood group A, AB, or B patients. Half of all gastric carcinomas and of proximal colon carcinomas showed complete loss of isoantigen, whereas the adjacent mucosa in these cases continued to express appropriate isoantigen. Isoantigen expression was completely lost in only 13% of pancreatic carcinomas tested. Neither A nor B isoantigen was detected in normal epithelium from the distal colon. By contrast, 85% of carcinomas derived from this site showed reexpression of isoantigen. Inappropriate expression of A isoantigen was detected in pancreatic carcinomas (2/5) but not in gastric or colon carcinomas (0/21). Inappropriate expression of B substance was not detected in any tissue (0/38). Interestingly, differential binding of antibodies to Type 1 versus Type 2 and/or difucosyl versus monofucosyl blood group B substances was manifested by differences in intensity of staining for endothelium and red blood cells.

ABO Blood-Group System↗

PubMed1984

Antigenic analysis of rabies and Mokola virus from Zimbabwe using monoclonal antibodies.

Eighteen strains of virus were recovered by tissue culture techniques from 20 samples of mouse brain received from Harare, Zimbabwe, and typed with monoclonal antibodies at The Wistar Institute. On the basis of reactivity with these monoclonal antibodies specific for rabies and rabies-related viruses, seven strains were identified as Mokola viruses, and the remaining 11, as rabies viruses. Seventeen of 36 monoclonal antibodies against the nucleocapsid antigen reacted with the Mokola strains, but none of 42 monoclonal antibodies against the glycoprotein that neutralized rabies virus was active against Mokola strains. Mokola virus was, however, neutralized by two monoclonal antibodies produced from mice immunized with Mokola, by a specific anti-Mokola serum prepared in rabbits, and to a lesser extent, by three polyclonal high titer antirabies sera of human or rabbit origin. Immunization of mice with a rabies vaccine (antigenic value, 10 international units) at a concentration 30-fold high than that necessary for complete protection against homologous challenge with rabies virus was not protective against Mokola infection. No cross-reactivity between Mokola and rabies viruses was seen with cytotoxic T lymphocytes.

Animals↗