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Z Steplewski

Publications and source records attributed to Z Steplewski.

At least 91 records · Page 5Linked to original sources
PubMed1987

Correlative studies on antigenicity of pancreatic cancer and blood group types.

Blood group-related antigenicity in 14 pancreatic cancer patients was examined by immunohistological method using monoclonal antibodies (MoAbs) against A, B, H, Lea, Leb, and CA 19-9 and compared with the phenotypic expression of the individuals' blood groups. MoAb-A reacted strongly with tumor tissue in four of five blood group A patients. Two of two patients with blood type B showed a weak, focal reactivity of their cancer with MoAb-B. H antigen was found in four of five patients from blood group A, while it was present in only one blood group O person and absent in B-type individuals. B antigen was inappropriately expressed in one person with type A blood and in two with type O. Lea antigen was expressed in all but two tumor tissues and Leb antigen in all tumorous tissues, irrespective of Le blood group status. MoAb 19-9 reacted with 11 of 14 cases.

ABO Blood-Group System↗
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

Total leukocytes, T cell subpopulation and natural killer (NK) cell activity in rats exposed to restraint stress.

Rats were stressed by immobilization for 3 hrs daily for 11 days and either sacrificed immediately after the last stress session (chronic stress group) or allowed to recover for 12 days and then sacrificed (recovery group). After 11 days of stress, leukocytes and lymphocytes were significantly decreased and neutrophils and large granular lymphocytes were markedly increased. The number of total, helper and suppressor T cells was significantly decreased but the percentage of T cells remained unchanged. Natural Killer (NK) cell activity was unaffected. After a 12 day recovery period from stress, the number of leukocytes returned to normal but the percentage of neutrophils was now below baseline whereas the percentages of lymphocytes and large granular lymphocytes had increased significantly. The number and percentage of total T cells and helper T cells was enhanced and NK cell activity tended to be increased. Thus, chronic stress as well as recovery from stress can affect individual components of the cellular immune system quite selectively and differently. In addition, a comparison of the effects of stress seen in this study with healthy rats with those seen under identical conditions in tumor bearing rats shows that stress or recovery from stress can affect the immune system differently in healthy or tumor bearing animals.

Animals↗
PubMed1986

Cytolytic interactions between murine macrophages, tumor cells, and monoclonal antibodies: characterization of lytic conditions and requirements for effector activation.

Because of recent successes in inducing the effective rejection of neoplasms in vivo by administration of monoclonal antibodies (MAb), we analyzed lytic interactions in vitro that occur between macrophages and several combinations of tumor targets and MAb that can lead to such successful immunotherapy. Murine macrophages, interacting with MAb of the IgG1, IgG2a, IgG2b, and IgG3 isotypes directed against SW-1116 carcinoma cells, destroyed the tumor targets efficiently over 24 to 48 hr in vitro. Lysis was dependent on both concentration of the MAb and density of the macrophages. Binding and lysis of the targets in the presence of MAb of the IgG2a isotype was dependent on intact Fc gamma 2aR on the macrophages; target binding was necessary but not sufficient for subsequent lysis. The lytic step appeared to have an oxidative basis, at least in part, as shown by inhibition of lysis with a nonspecific scavenger of H2O2 or under either anaerobic or glucose-deprived conditions. TG-elicited or pyran-elicited macrophages, which are incompletely activated for antibody independent kill of tumor cells, were effective in mediating ADCC. By contrast, macrophages fully activated for direct cytolysis by administration of BCG or Propionibacterium acnes in vivo or by MAF and LPS in vitro, had diminished capacity for ADCC. A spectrum of five other tumor cells and antibodies, four of which are also involved in successful models of immunotherapy in vivo, were also killed over 48 hr more effectively by thioglycolate-elicited than by BCG-activated macrophages. Taken together, the data indicate that macrophages can lyse tumor cells in an ADCC reaction that has application to some models of the destruction of tumors in vivo, but that the lysis is slow and requires the macrophages to be activated in a specific way(s).

Animals↗
PubMed1986

Monoclonal antibody-defined antigens of human prostate cancer cell line PC3.

Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 125I-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity.

Animals↗
PubMed1986

Presence of two distinct acinar cell populations in human pancreas based on their antigenicity.

The immunohistochemical localization of ABH- and Lewis (Le)-related blood group antigens, including CA 19-9, a sialylated Lea antigen, was examined using monoclonal antibodies (MoAbs) in 18 normal human pancreases and compared with ABH blood group antigenicity of the individuals. Acinar cells expressed ABH, Leb, Ley, and in some cases, Lex antigen in various proportions, but not Lea and CA 19-9. The reactivity of Leb and Ley was similar with regard to cellular localization and specificity. In all specimens but one, the distribution of Leb (and Ley) and H antigens on the one hand, and of A or B antigens on the other, showed a reciprocal relationship, in that one group of acini expressed Leb (and Ley) and H antigens, but lacked any A or B antigens (type 1 acinar cell); another group of acinar cells had A or B antigens, but expressed neither Leb (Ley) or H antigens (type 2 acinar cell). In ductal cells, four of eight individuals with blood group A, two of three with blood group B, and five of six with blood group O expressed the appropriate antigen, while the remainder did not. Lea antigen was expressed primarily by centroacinar and terminal ductular and ductal cells of medium-sized ducts of all specimens, whereas Leb was present in the cells of small and large ducts in all but four cases. The reactivity of ductal and ductular cells to Lex was negative, except for one case. MoAb-Ley and MoAb 19-9 reacted only with a few ductal cells in six (33%) and 12 cases (67%), respectively. There was no relationship in the expression of Le-related antigens between acinar and ductal/ductular cells; nor were there any sex difference with regard to the binding patterns of any antibodies. However, age appeared to influence the reactivity of some antibodies with acinar cells. Islet cells did not react with any of the antibodies. The results indicate that, although the antigenicity of epithelial cells can be affected by the host blood group types, there might be several regulatory systems for expression of blood group antigens in a cell-specific pattern.

Adolescent↗
PubMed1986

Blood-group antigen expression during pancreatic cancer induction in hamsters.

The expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters with N-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and the beta-subunit of human chronic gonadotropin (beta-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and beta-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.

Adenocarcinoma↗
PubMed1986

Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody-dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17-1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis.

Adenocarcinoma↗
PubMed1986

Treatment of advanced measurable or evaluable pancreatic carcinoma with 17-1A murine monoclonal antibody alone or in combination with 5-fluorouracil, adriamycin and mitomycin (FAM).

Between 1/85 and 3/86, 16 patients with advanced measurable or evaluable pancreatic carcinoma were treated with mouse monoclonal antibody consisting of a single dose of 400 mg 17-1A immunoglobulin given intravenously. None of the eight patients who received monoclonal antibody alone had any subjective or objective benefit. Two of the eight patients who received a combination of monoclonal antibody and 5-fluorouracil, adriamycin and mitomycin (F.A.M.) chemotherapy had clinically useful partial responses lasting 11 months and 7 months respectively. One of these patients, whose initial treatment consisted of an 8-week cycle of F.A.M. chemotherapy, had progressive deterioration as evidenced by weight loss and persistent abnormality of his CT scan, and then achieved a partial response following a single injection of monoclonal antibody while chemotherapy was continued. His response lasted 11 months. There was no toxicity associated with the administration of monoclonal antibody, and the F.A.M. chemotherapy was well-tolerated with moderate and acceptable hematologic toxicity and mild gastrointestinal side effects. There were no treatment-related deaths.

Adult↗
PubMed1986

Clinical trial of Wistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report.

Immunotherapy using monoclonal antibody 17-1A has been performed on 22 patients with metastatic gastrointestinal cancer. Criteria for treatment included objective evidence of advanced colon, gastric, or pancreatic cancer (positive CAT scan or x-rays, elevated tumor markers, and/or abnormal liver function tests). The tumor tissue was antigenically positive in all cases. Performance status ranged from 50 to 100%. No adverse reactions were noted. Of the 22 cases treated, 4 (18%) have died, none have rapidly progressive disease, 4 (18%) have slowly progressive disease, 10 (45%) are considered stable with disease, and none are considered partial or complete responses. It is too early to classify the response in 4 cases. In 6 of 8 patients where anti-idiotypic data was available, death or progressive disease was correlated to negative anti-idiotypic response, and clinical stability to a positive anti-idiotypic response. In the patients considered to be stable, the percent change from pre-treatment serum 19-9 concentrations to current values ranged from -10% to +353%. In the patients who have died or have been classified as slowly progressive the serum 19-9 changes ranged from +13% to +707%.

Adenocarcinoma↗
PubMed1986

Detection of murine immunoglobulin in human tissues following therapeutic infusion of monoclonal antibody.

A class switch variant of hybridoma CO19-9 secreting IgG2a antibodies was shown to have the same immunoperoxidase binding pattern in human tissue as the IgG1 antibody secreted by the parental hybridoma. The IP tissue binding of GA73.3 and 17-1A monoclonal antibodies which have been suggested to bind to structurally related antigens were compared; although quite similar in distribution, some differences were noted. GA73.3 bound to 12/12 colon carcinomas compared to 17-1A which reacted with 11/12 tumors. In several cases, the percentage of cells reactive with GA73.3 (90-100%) exceeded those reactive with 17-1A (10-25%). Additionally, the intensity of reactivity for GA73.3 was consistently greater than that seen with 17-1A. The detection of murine antibody bound to human tissues following therapeutic infusion of 19-9 IgG2a or GA73.3 differed. Detection of antibody-antigen complexes was seen less often in patients who had received 19-9 IgG2a (2/6) than in patients who had received GA73.3 (5/5). Additionally, the presence of murine immunoglobulin was seen only in the extracellular mucin of the patients receiving 19-9 IgG2a, whereas strong cellular binding of murine immunoglobulin was noted following infusion with GA73.3.

Animals↗
PubMed1986

Trial of therapy with monoclonal antibody 17-1A in pancreatic carcinoma: preliminary results.

Monoclonal antibody 17-1A was administered to 25 patients with advanced unresectable carcinoma of the pancreas. Ten patients received 17-1A alone in 400 mg doses delivered intravenously, while 15 patients received 400 mg 17-1A absorbed on to autologous peripheral blood mononuclear cells collected by leukapheresis (usual yield greater than 10(9) cells). No toxicity was observed. Twenty-three patients developed circulating anti-murine immunoglobulin within three weeks of treatment, and 11 patients developed circulating anti-idiotypic immunoglobulin. Four out of 19 clinically evaluable patients (21%) showed objective regressions of tumor. Response did not correlate with the presence or absence of anti-idiotypic antibody and did not correlate with the method of treatment with 17-1A alone or 17-1A and mononuclear cells, at the time of current analysis.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibody CO17-1A and leukapheresis in immunotherapy of pancreatic cancer.

Eighteen patients with measurable or evaluable advanced (metastatic or unresectable) adenocarcinoma of the pancreas were treated with a single infusion of monoclonal antibody CO17-1A in autologous leukocytes. No toxicity was experienced with treatment. Three of seventeen patients evaluable for response demonstrated unusually stable disease and a decrease in serum CA 19-9 antigen in two patients who expressed this biomarker. Human anti-mouse antibody developed in 81% of these patients. Monoclonal antibody CO17-1A may have a cytostatic effect in a small fraction of patients. Future clinical trials will focus on enhancing this effect with other immune modulators.

Adenocarcinoma↗
PubMed1986

Identification and characterization of the CO17-1A carcinoma-associated antigen.

The cell surface antigen defined by monoclonal antibody CO17-1A is sensitive to proteinase K but not to neuraminidase digestion. Immunoprecipitation of two polypeptide chains of 30 and 40 kDa using large amounts of CO17-1A antibody confirmed that the CO17-1A antigen is a protein. The requirement for large quantities of CO17-1A antibody may relate to the binding properties of this antibody, as bivalent but not monovalent (Fab) forms of the antibody bind effectively to carcinoma cells. The 30 kDa form of the CO17-1A antigen was purified by immunoaffinity chromatography using GA733, another monoclonal antibody that recognizes the CO17-1A antigen. Treatment of purified antigen with endoglycosidase F revealed a 25 kDa and a 28 kDa species, demonstrating that the antigen has at least two N-linked oligosaccharide chains. Protease treatment of the purified antigen revealed a 26 kDa protease-resistant polypeptide.

Antibodies, Monoclonal↗