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Z Steplewski

Publications and source records attributed to Z Steplewski.

At least 55 records · Page 3Linked to original sources
PubMed1990

Radioactive gold cluster immunoconjugates: potential agents for cancer therapy.

An 11 gold atom (undecagold) cluster was covalently attached to specific sites on Fab', F(ab')2 and whole IgG molecules such that each carried 11-33 gold atoms without significant loss of native immunospecificity. Gold cluster labeled 17-1A monoclonal F(ab')2 antibody fragments showed 80% immunoreactivity compared to native antibody fragments in binding to human colon carcinoma cells in vitro. Radioactive gold in vivo biodistributions in nude mice with human tumors are also reported. By using clusters, potentially a larger destructive payload can be carried per antibody.

Animals↗
PubMed1990

Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture.

Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist.

ABO Blood-Group System↗
PubMed1990

Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens.

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.

Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins. Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system. A 1.4-kilobase cDNA species was enriched by immunoselection with monoclonal antibody. The authenticity of individual clones was established by immunologic and sequence criteria. At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4. The amino acid sequence derived from the previously described GA733-related gene, GA733-1, was found to be 49% identical to GA733-2. The positions of 12 cysteine residues in the extracellular domains of the two GA733 antigens are conserved, as is the overall distribution of hydrophobic and hydrophilic residues. A 1.45-kilobase transcript of the GA733-2/KSA gene was found to be expressed in cell lines derived from colorectal and pancreatic carcinoma.

Amino Acid Sequence↗
PubMed1990

Oligosaccharide Y specific monoclonal antibody and its isotype switch variants.

Isotype switch variants of the IgG3 secreting hybridoma BR55-2 were developed with gamma 1, gamma 2b and gamma 2a heavy chains. The variants have the same affinity for antigen and expected affinities for the Fc receptor. The Y antigen defined by MAb BR55-2 has a restricted distribution to breast, colorectal, pancreatic, gastric and small cell lung carcinomas. The MAb BR55-2 also bound to prostatic and laryngeal carcinomas. The BR55-2 defined epitope is expressed by gastrointestinal cancer cell lines as a glycolipid, while the breast carcinoma cells express the same epitope on glycoproteins. These differences may influence tumor cell susceptibility to lysis by MAb BR55-2 and its isotype switch variants.

Animals↗
PubMed1990

Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects.

Thirty patients with advanced measurable pancreatic adenocarcinoma were entered onto a phase II trial with recombinant interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and monoclonal antibody (Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following interferon infusion). The effect of a single interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC), Fc receptor occupancy by antibody, and human leukocyte antigen-DR (HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II fever, nausea and vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic adenocarcinoma using this dose and schedule of interferon gamma and Mab 17-1A. Future trials will focus on alternate schedules of Mab 17-1A with the hope of improving tumor antigen saturation and circulating levels of infused antibody.

Adenocarcinoma↗
PubMed1990

Disaccharidases activity in the intestinal mucosa after methotrexate therapy.

Disaccharidases activity in the intestinal mucosa samples of rats was examined after intragastric and intramuscular methotrexate therapy. Methotrexate was given on a twice a week schedule (1 mg/kg body weight). The animals were sacrificed after 2 weeks, 1 month, and 2 months of this therapy. A statistically significant but transient decrease of the lactase and maltase activity was found. The authors suggest studying the beneficial effect of low disaccharidase diet in the first period of methotrexate therapy in children treated with methotrexate.

Administration, Oral↗
PubMed1990

Alterations in monoclonal antibody affinity and antigenic receptor site expression on mycoplasma-infected human colorectal cancer cells.

The affinity of MoAb CO 17-1A and expression of its antigenic target were studied on uninfected and mycoplasma-infected colorectal cancer cell lines SW 1116 and SW 948. Binding of 125I-labeled CO 17-1A to SW 1116 cells was quantified at 37 degrees C by determination of the affinity constant (Ka) and the number of antigenic receptor sites (r) per cell using Scatchard plots. When mycoplasma-free SW 1116 cells were used as targets, Ka was 0.92 +/- 0.06 x 10(8) M-1 and r = 1.32 +/- 0.14 x 10(6) at 37 degrees C. One batch of unspeciated, mycoplasma-infected SW 116 cells had reduced affinity and a decreased number of antigenic receptor sites per cell for 125I-labeled 17-1A, while another batch of infected SW 1116 cells had a 4- to 5-fold increase in r and diminished Ka for the antibody compared with uninfected cells. When unspeciated, mycoplasma-infected SW 948 cells were exposed to 125I-labeled 17-1A and the data subjected to Scatchard analysis, the affinity of the antibody deviated markedly from linearity and rendered analysis for Ka and r meaningless. These data indicate that mycoplasma infection can produce variable effects on the cellular expression of antigenic receptor sites and the affinity of antibody for its target, and emphasize the importance of using mycoplasma-free cell lines in studies of these parameters.

Animals↗
PubMed1990

Development of a new radiolabel (203Pb) and new chelating agents for labeling monoclonal antibodies for imaging.

High liver uptake and slow body clearance presently limit the usefulness of 111In labeled antibodies for tumor imaging. We have investigated 203Pb as an alternative and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A, were labeled (bicyclic anhydride method) with 203Pb and 111In with 60 and 90 per cent labeling yields, respectively. The biodistribution of 203Pb-17-1A conjugates was compared with the corresponding 111In-labeled preparations and with 203Pb-DTPA, 203Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24 and 96 h. 203Pb labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared with indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2-diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium.

Animals↗
PubMed1989

Selective chromosomal damage and cytotoxicity of 125I-labeled monoclonal antibody 17-1a in human cancer cells.

A monoclonal antibody, 17-1a, which reacts with antigen expressed in human colon cancers was radiolabeled in high specific activity with 125I. The combination of the antibody and this radionuclide was observed to elicit specific cellular damage after being internalized into cells of the SW1116 human colon cancer cell line. The degree of internalization was quantitatively measured and found to increase over time to 49% after a 48-h incubation period. During this period, significant chromosome aberrations were observed in the SW1116 cell line due to the Auger electrons of 125I. This damage was not observed using Na125I, a nonimmunoreactive radiolabeled antibody, or cells which did not contain the requisite antigen. The number of chromosomal aberrations increased with increasing radioactive concentration of 125I-17-1a. The nuclear damage resulted in specific cellular cytotoxicity and decreased cell survival of SW1116 cells exposed to various concentrations of 125I-17-1a.

Antibodies, Monoclonal↗
PubMed1989

Inhibition of metastases of a human melanoma xenograft by monoclonal antibody to the GD2/GD3 gangliosides.

A human melanoma variant cell line was obtained from a lung metastasis that arose spontaneously after we inoculated melanoma cells sc into a nude mouse. In this model, IgG2a monoclonal antibody (MAb) ME 36.1 defining the GD2/GD3 gangliosides inhibited melanoma growth at the primary site and metastatic spread of the cells, whereas an IgG1 variant of MAb ME 36.1 inhibited lung metastasis formation only. Possible mechanisms of antitumor effects of MAb ME 36.1 are discussed.

Animals↗
PubMed1989

Colon carcinoma-associated glycoproteins recognized by monoclonal antibodies CO-029 and GA22-2.

Two murine monoclonal antibodies (MAb) CO-029 and GA22-2 are described which reacted specifically with the human gastrointestinal tumor cell lines LS180 and SW1222, respectively. CO-029 specific antigen was found by immunoprecipitation and Western blotting to be a highly expressed protein consisting of a single polypeptide chain of 32kDa. The gastric tumor associated antigen GA22-2 was a 185kDa polypeptide which did not comigrate with the 180 kDa carcinoembryonic antigen (CEA), neither was it immunologically crossreactive with the latter. Both CO-029 and GA22-2 antigens were shown to be glycosylated by their retention on Sepharose-lectin columns. CO-029 was highly bound by wheat germ agglutinin indicating the accessibility of N-acetylglucosamine or N-acetyl-neuraminic acid residues. GA22-2 showed higher specificity to soybean agglutinin inferring the preferential accessibility of galactose or N-acetylgalactosamine-like residues on its saccharide moiety.

Animals↗
PubMed1989

Monoclonal antibodies as applied to tumor-associated antigens: the CO17-1A antigen.

The development of antitumor MAbs has led to the identification of many TAAs but no TSAs. It now seems unlikely that there are antigens exclusively associated with any tumor type. Nonetheless, there are numerous applications of the antitumor MAbs. They are used in serum assays to monitor tumor burden and in histologic assays to identify the tumor type. Initial attempts to use MAbs therapeutically have benefited some patients, but much work is needed to better understand the mechanism and to enhance this tumoricidal effect. Finally, the antitumor MAbs will allow biochemical and genetic analyses of the roles of TAAs in tumor progression.

Animals↗