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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 307 records · Page 17Linked to original sources
PubMed1983

Interactions of preimplantation mouse embryos with reovirus serotypes 1 and 3.

Mouse two-cell embryos were infected in vitro with reovirus serotypes 1/Lang and 3/Dearing, and the embryos were either implanted into pseudopregnant mice or observed in vitro for cytopathic effects. The reovirus serotypes 1/Lang and 3/Dearing differed in their capacity to kill embryos in vitro and in vivo: when embryos were infected in vitro with reovirus serotype 1/Lang and then transferred to foster mothers, pups resulted only at multiplicities of infection of a few particles per embryo. In contrast, infection of embryos with as much as 6 X 10(4) reovirus type 3 particles per embryo resulted in viable pups. In vitro, reovirus serotype 1/Lang was more virulent than serotype 3/Dearing. The infection of ovum with reovirus offers a unique model for the study of congenital infection and should yield important information concerning the molecular basis of virus virulence to maturing fetuses.

Animals↗
PubMed1983

Anti-idiotypic antibodies induce neutralizing antibodies to rabies virus glycoprotein.

Rabbit anti-idiotypic antibodies (alpha Id Ab) were prepared against five murine monoclonal antibodies (mAb) specific for the rabies virus glycoprotein. Four of the mAb were directed against three known, type-specific, neutralizing sites on the glycoprotein, and the other mAb was directed against a topographically uncharacterized, nonneutralizing epitope. An absence of significant cross-reactivity among the alpha Id Ab for heterologous mAb suggested that the alpha Id Ab were highly specific for unique variable region determinants. The binding of three of the five alpha Id Ab to their homologous mAb could be inhibited by rabies virus-soluble glycoprotein, suggesting that the alpha Id Ab possessed subpopulations similar or adjacent to the antigen-binding site of the mAb. Two of the five alpha Id Ab injected into mice elicited a specific virus-neutralizing antibody response. Mechanisms to account for the induction of the virus-neutralizing antibody by alpha Id Ab are discussed.

Animals↗
PubMed1983

Metastatic colon carcinoma detected with radiolabeled F(ab')2 monoclonal antibody fragments.

Nine patients with colonic carcinoma were studied with I-131-labeled F(ab')2 fragments of an anti-colorectal carcinoma monoclonal antibody. A total of 69% of colon cancer sites were detected without background subtraction; metastases from a concurrent breast carcinoma in one patient were not seen. Lesions ranged from 1.5 to 8 cm. The mean thyroid uptake of I-131 at 24 hours was 0.25%. Half-lives of I-131 in the blood (protein-bound and total) fit a two-compartment model, with half-lives of 3.5 and 27.6 hours for the protein-bound fraction and 3.6 and 23.8 hours for total I-131. Using quantitative methods, a mean value of 0.0047%/cm3 of the administered dose was localized in the tumor at peak concentration, which occurred approximately 48 hours post-administration. This has implications for therapy planning.

Antibodies, Monoclonal↗
PubMed1983

Production and characterization of monoclonal antibodies against human malignant melanoma.

The specific immunoreactivities of 31 monoclonal antibodies against human malignant melanoma were analyzed on a variety of malignant and nonmalignant human cells. Seven distinct groups were defined based on reactivity in radioimmunoassay and in mixed hemadsorption assay. The Group A antibody bound to 33% of short- and long-term cultured melanomas; Group B antibodies reacted with the majority of melanomas, astrocytomas, neuroblastomas, and fetal polygonal cells; and Group C antibodies bound to melanomas, teratocarcinomas, and to melanocytes grown in the presence of tumor-promoting phorbol esters. Antibodies of Groups D-G showed a less restricted binding pattern. In all groups, antibodies of IgG2b and IgM isotypes mediated complement-dependent lysis (CDC) and antibodies of IgG1, IgG2a, and IgG2b isotypes mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Biochemical analysis indicated that 16 different proteins with molecular weights ranging between 28,000 and 500,000 were detected by the monoclonal antimelanoma antibodies.

Antibodies, Monoclonal↗
PubMed1983

Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin.

Monoclonal antibody 19-9, produced by a hybridoma prepared from spleen cells of a mouse immunized with a human colon carcinoma cell line, detects an antigen in the serum from most patients with gastrointestinal and pancreatic cancer (M. Herlyn, H.F. Sears, Z. Steplewski, and H. Koprowski, J. Clin. Immunol., 2: 135-140, 1982). The epitope of this antibody is a carbohydrate with the sugar sequence (formula; see text) in which NeuNAc is N-acetylneuraminic acid, Gal is galactose, GlcNAc is N-acetylglucosamine, and Fuc is fucose. In the colon carcinoma cell line and many gastrointestinal and pancreatic cancers, this sequence occurs in a monosialoganglioside containing a sialylated Lea-active pentasaccharide (sialylated lacto-N-fucopentaose II, IV3-alpha-NeuNAc-III4-alpha-Fuc-LcOse4, in which LcOse4 is Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc) (J. L. Magnani et al. J. Biol. Chem., 257: 14365-14369, 1982). However, the antigen in the sera of patients occurs mainly as a mucin, not a ganglioside, based on the following evidence. Little antigen is extracted by organic solvents from sera, and that which is extracted remains at the origin under conditions of thin-layer chromatography where the ganglioside antigen migrates up the plate. Upon gel filtration of serum on Sephacryl S-400, the antigen is eluted in the void volume, indicating a molecular weight of greater than or equal to 5 X 10(6). Incubation for 5 hr at 37 degrees in 0.1 N NaOH destroys the serum antigen but does not affect the ganglioside antigen. The density of the serum antigen as determined in a CsCl gradient is 1.50 g/ml, while in 4 M guanidine. HCl its density is 1.43 g/ml. Finally, antigen affinity purified by antibody 19-9 from the serum of a cancer patient belonging to the Le(a-b+) blood group contains Leb antigen, consistent with the multiple antigenic specificities exhibited by mucins.

Antibodies, Monoclonal↗
PubMed1983

Radioimmunodetection of human tumor xenografts by monoclonal antibodies.

Mouse IgG2a monoclonal antibodies with specific binding reactivity in vitro to human tumors of the gastrointestinal tract were radioiodinated and injected into immunosuppressed mice xenografted with human colon carcinoma tumors. The antibodies preferentially localized in tumor tissue compared to normal mouse tissue, as determined by differential tissue counting of radioactivity. Preferential antibody localization in tumor tissue was greatly enhanced when F(ab')2 fragments of the antibodies were used, and the fragments localized specifically only in those tumors that bind the antibodies in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus monoclonal antibody of the same isotype as the specific antibody did not localize in tumors. Tumors could be located by whole-body gamma-scintigraphy with radiolabeled specific antibody F(ab')2 fragments without background subtraction.

Animals↗
PubMed1983

Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with a practical concentration (300 micrograms/ml) of antibody to human albumin (Ab) and 1083 17-1A monoclonal colorectal antibody (MAb-17-1A) via an acylation reaction using cyclic DTPA anhydride (cDTPAA). The conjugation reaction was favored as pH increased. Bicarbonate buffer at pH 8.2 was chosen for studies of the effect of the cDTPAA-to-antibody ratio on DTPA conjugation with antibody because of its good buffer capacity at that pH. The reaction of cDTPAA with Ab at molar ratios of 2000, 1000, 500, and 100 in the bicarbonate buffer gave rise to 11, 9, 8, and 2 indium atoms incorporated per Ab with 47%, 55%, 59%, and 77% retention of the binding activity. For the conjugation reaction of MAb-17-1A, 29, 28, 31, 11, 4, and 1 indium atoms were incorporated, with the retention of less than 5%, less than 5%, less than 5%, 12%, 60%, and 93% of binding activity when the molar ratio was 5000, 2000, 1000, 500, 100, and 50.

Animals↗
PubMed1983

A preliminary trial of vaccinia oncolysates in the treatment of recurrent melanoma with serologic responses to the treatment.

A preliminary trial was designed as a toxicity/feasibility study using a fixed dose of vaccinia melanoma oncolysates (VMO) to treat recurrent stage II and stage III (skin, subcutaneous, and nodal metastases only) melanoma. There were no adverse consequences of the therapy, and 4 of the 12 patients treated seemed to have responded to the treatment by the criteria of the study. Sera from the six patients with the longest survival showed immunoreactivity to human melanoma lines in a Staphylococcus protein A assay (SpA) after 3 months of therapy. While the specificity of this immunoreactivity remains to be determined, the discovery of posttreatment serologic activity in a SpA assay permits investigation of the degree of VMO immunostimulation at different dose levels of the biologic. This assay may provide the means to quantitate optimal biologic dose for future melanoma oncolysate trials. The Southeastern Cancer Study Group is now conducting a phase I/II trial with these vaccinia melanoma oncolysates using the SpA assay to monitor this trial.

Antibodies, Neoplasm↗
PubMed1982

A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II.

Two monoclonal antibodies produced by hybridomas obtained from a mouse immunized with a colorectal carcinoma cell line bind specifically to human gastrointestinal cancer cells. The antigen of this antibody in the carcinoma cell line, a monosialoganglioside, has been isolated. Its carbohydrate structure is probably (formula: see text). This oligosaccharide is a sialyl derivative of lacto-N-fucopentaose II, a hapten of the human Lea blood group antigen. About 30 micrograms of ganglioside is obtained from 1 g of cells, wet weight. The ganglioside was detected by autoradiography in lipid extracts of some carcinomas and of meconium, but not in lipid extracts of normal adult tissues. Antigen was detected by solid phase radioimmunoassay in lipid extracts from 12 out of 21 adenocarcinomas of the colon, from 4 out of 5 gastric adenocarcinomas, and from 4 out of 7 pancreatic carcinomas. Antigen was not detected in lipid extracts from 5 esophageal carcinomas or from normal colon and gastric mucosa, pancreas, kidney, liver, and bone marrow.

Animals↗
PubMed1982

Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours.

A phase-I clinical trial of a murine monoclonal antibody that specifically suppresses growth of human gastrointestinal tumours in athymic mice was conducted in four patients, who were given 15-200 mg purified antibody. The monoclonal antibody persisted in the circulation for more than a week when more than 15 mg was given. Antibodies against mouse immunoglobulin developed in three of the four patients. In one patient who received autologous mononuclear cells that had been mixed with monoclonal antibody by way of a hepatic-artery catheter, hepatic metastases became smaller and their echogenic characteristics changed, and there was heavier monocyte infiltration in the histological appearance of a resected metastasis.

Adenocarcinoma↗
PubMed1982

Ex vivo perfusion of human colon with monoclonal anticolorectal cancer antibodies.

The binding of mouse hybridoma monoclonal antibodies directed against human colon carcinomas was studied using an ex vivo perfusion model of a freshly resected human colon segment containing a carcinoma. Tumor and the surrounding normal bowel is exposed to the putative tumor antigen through an intact vascular system without mechanical or enzymatic cellular alteration. An hour of perfusion was conducted on thirty specimens using five different monoclonal anticolorectal cancer (ACRC) antibodies. Three were gamma 1, one gamma 2A and one was IgM isotype. Control anti-influenza virus monoclonal antibodies were used to demonstrate absence of nonspecific binding. Our antibody 17-1A bound to the colon cancer in seven of ten trials, but bound to normal colon cells also in four of these trials. The IgM antibody did not bind to anything. The two gamma 1 antibodies that recognize an antigen shed from the surface of the cell did not demonstrate cell binding under conditions of this study, and conditions to detect this will have to be modified. The ex vivo perfusion model as performed in this study can provide a valuable adjunct to evaluate the potential clinical utility for antibody conjugate radiolocalization or therapy of colon cancer.

Adenocarcinoma↗
PubMed1982

Monoclonal antibody detection of a circulating tumor-associated antigen. I. Presence of antigen in sera of patients with colorectal, gastric, and pancreatic carcinoma.

Hybridoma-secreted monoclonal anti-colorectal carcinoma antibodies 19-9, 52a, and C4 14 bind specifically to cells of colorectal, gastric, and pancreatic carcinoma in tissue culture. The assay for the detection of antigen in human sera is based on the inhibition of binding of monoclonal antibodies to target preparations of colorectal carcinoma cells. Binding of monoclonal antibody 52a was inhibited more than 12% by 163 of 255 sera from patients from various stages of carcinoma of colon and rectum, by 45 of 49 sera from patients with pancreatic carcinoma, and by 8 of 11 sera from patients with gastric carcinoma. By contrast, only 7 of 89 sera from patients with other malignancies and 2 of 108 sera from healthy donors inhibited binding of this monoclonal antibody by more than 12%. These studies show the potential usefulness of monoclonal antibodies in the diagnosis of human malignancy.

Adult↗
PubMed1982

Monoclonal antibody detection of a circulating tumor-associated antigen. II. A longitudinal evaluation of patients with colorectal cancer.

An antigen identified by two monoclonal anti-colorectal cancer antibodies was studied in sera of 85 patients who had a resection of their primary colorectal cancer. Preoperative and postoperative serum samples and sera collected every 3 months for at least 1 year were included in this study. The levels of these antigens were compared to the carcinoembryonic antigen (CEA) levels. Sixty-six patients had at least one antigen elevated in the preoperative period. Malignancy recurred in 10 patients. In 8 of these the recurrence could have been predicted by the persistence or rise in antigen levels 3 to 18 months prior to the detection of the recurrence by current clinical methods. The data suggest that the assays for these antigens are valuable prognostic aids for making clinical therapeutic decisions and appropriately stratifying patients for clinical trials.

Aged↗