Zenon Steplewski - Academia.edu (original) (raw)

Papers by Zenon Steplewski

Journal of Infectious Diseases, 2015

This review describes the development of monoclonal antibodies and the inception of their use in ... more This review describes the development of monoclonal antibodies and the inception of their use in cancer therapy, their impact on defining cancer biomarkers, and their structural utility in new cancer vaccine development.

The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmuno... more The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmunoassay, mixed-hemadsorption assay, and quantitative absorption on a variety of malignant and nonmalignant cells. Three of the six hybridoma-secreted antibodies bound to the majority of melanoma cell lines, melanoma tumors, and astrocytoma cell lines as well as to all normal and Epstein-Barr virus-transformed lymphocytes tested. The binding pattern coincides with the presence or absence of the DR antigen on human cells. Conversely, two other antibodies, 19-19 and Nu4B, detected two different antigens common to melanoma and astrocytoma cells only. Cloning of melanoma cells resulted in establishment of DR-positive and DR-negative clones, with the binding of Nu4B antibody retained in all.

Hybridoma, 1992

The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of... more The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of antigenic receptor sites (r) and the affinity constant (Ka) of monoclonal antibody CO 17-1A IgG were studied on two human colorectal cancer cell lines, CX-1 and SW 1116. Cells were incubated with varying concentrations of rHuIFN-alpha 2b prior to exposure to 125I-labeled 17-1A IgG at 37 degrees C following which r and Ka were determined by means of Scatchard plots. Varying concentrations of rHuIFN-alpha 2b had significant growth inhibitory effects on CX-1 and SW 1116 cells, which were time and concentration dependent, but no effects on expression of r and Ka compared to controls. Our data indicate that rHuIFN-alpha 2b does not invariably increase the expression of tumor-associated antigens and that this effect may be independent of its antiproliferative activity. The in vitro response or lack thereof of neoplastic cells to rHuIFN-alpha 2b may be useful to identify those patients who potentially might gain from a clinical course of rHuIFN-alpha 2b for either therapeutic or diagnostic purposes.

The American Journal of Pathology, Jun 1, 1982

The use of antimelanoma monoclonal antibodies on tissue sections using a two-step indirect immuno... more 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&amp;#39;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.

Journal of Biological Response Modifiers, Feb 1, 1984

Twenty patients with metastasis of gastrointestinal malignancies were treated with an anti-colore... more 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.

Cancer Research, Jun 1, 1984

Early culture supernatants from hybridomas that were ob tained through fusions of mouse myeloma c... more Early culture supernatants from hybridomas that were ob tained through fusions of mouse myeloma cells with lymphocytes of melanoma-immunized mice were screened for their reactivity with a paraffin-embedded cell block of a melanoma cell line, using a biotin:avidin immunoperoxidase procedure. Eleven monoclonal antibodies were derived that define several new melanomaassociated antigens. The antigens include a neutral glycolipid, gangliosides, membrane-associated proteins, cytosolic proteins, and strongly secreted proteins. These antibodies, which detect antigens that withstand tissue fixation and embedding proce dures, were tested for reactivity in fixed cell lines, as well as in melanoma biopsies. These antibodies may provide powerful tools in diagnostic studies of human malignant melanoma biopsy material.

Four major carcinoembryonic antigen-related glycopeptides (Mr 180,000, 160,000,000,000) were dete... more Four major carcinoembryonic antigen-related glycopeptides (Mr 180,000, 160,000,000,000) were detected in SW948 colon carcinoma cells and in colon adenocarcinoma tissue using a monoclonal antibody (C420-32) generated by immunizing mice with SW1222 human colon carcinoma cells.

Proceedings of the National Academy of Sciences, Sep 1, 1968

We have previously reported' activation of infectious SV40 in transformed cell types of various o... more We have previously reported' activation of infectious SV40 in transformed cell types of various origins after fusion with susceptible African green monkey kidney cells (AGMK). In the same report, we described failure to activate SV40 after fusion of AGMK cells with two sublines of SV40-transformed human cells (W98-VaC and WI26Va4) and cultures originating from four clones of SV40-transformed green monkey kidney cells (GMK-EVa).

Nuclear Medicine Review Central Eastern Europe Journal of Bulgarian Czech Macedonian Polish Romanian Russian Slovak Yugoslav Societies of Nuclear Medicine and Ukrainian Society of Radiology, Feb 1, 2002

BACKGROUND: In this paper we present the preliminary results of a prospective trial of the effica... more BACKGROUND: In this paper we present the preliminary results of a prospective trial of the efficacy of simultaneous radiotherapy and anti-EGFR 125 I radioimmunotherapy of malignant gliomas with 2 years' total survival as the end-point, raising the question whether anti-EGFR 125 I radioimmunotherapy influences the disease-free survival in these patients. MATERIAL AND METHODS: Patients with anaplastic astrocytoma or primary glioblastoma were previously treated by a mac-roscopically radical neurosurgical approach and randomized either to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven patients were included in the group with radioimmunotherapy, among them five with GBM and two with AA, and five patients in the control arm. Patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques. Anti-EGFR 125 I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was started during 4 th week of radiotherapy and was repeated three times in one week intervals. RESULTS: Time of follow-up ranges between 2 and 10 months in the anti-EGFR 125 I radioimmunotherapy arm and 4 and 9 months in the control arm. Recurrence was diagnosed in all patients in the EGFR 125 I group with a lethal outcome in two of them and in 4 patients in the control group. Median time to recurrence was 2 and 5 months respectively. CONCLUSIONS: Taking into account early recurrences observed, we propose to continue the studies on the efficacy of adjuvant anti-EGFR 125 I radioimmunotherapy in a selected group of patients in whom the greatest benefit may be expected on the basis of molecular studies, among them EGFR expression investigation.

Cancer Research, Nov 1, 1985

A murine monoclonal antibody (MAb) which binds to human metastatic gastrointestinal adenocarcinom... more A murine monoclonal antibody (MAb) which binds to human metastatic gastrointestinal adenocarcinomas can be adminis tered safely and has tumor effects in some patients. Its thera peutic effect was assessed in 20 patients with measurable advanced colorectal carcinoma that was refractory to prior sur gical resection, chemotherapy, and/or radiotherapy. All patients had agreed to receive no other therapy at the time of MAb administration and follow-up evaluation. In one patient, tumor at all known sites responded after a single i.v. injection of antibody. One other patient had a marked reduction in a hepatic metastasis where binding of 131l-labeled F(ab')2 MAb fragments was dem onstrated but not in his abdominal wall mÃ©tastases where no MAb binding could be demonstrated. In a third patient, stabili zation persisting for 12 mo of an aggressively growing tumor was observed. The antibody was well tolerated in all patients, although 10 patients mounted an anti-murine immunoglobulin antibody response.

Transplantation Proceedings, Oct 1, 1980

Cancer Immunology and Immunotherapy, 1990

Fifteen patients with metastatic gastrointestinal adenocarcinomas were treated with low doses of ... more Fifteen patients with metastatic gastrointestinal adenocarcinomas were treated with low doses of recombinant human interferon y (rh-IFNy) and a mixture of monoclonal antibodies (mAb) that bind to tumor cells. All antibodies were of the IgG2a isotype and interact with human effector cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Natural killer lysis against K562 cells by peripheral blood mononuclear cells purified from patients' blood was enhanced in all patients at day 3 during IFNy treatment. Monocytes from two patients had increased ADCC levels. Increase in the percentage of monocytes able to bind mouse IgG2a was detected by Fc receptor flow cytometry analysis 24 h after the first IFNy infusion. However, 3 days later, the percentage of fluorescent cells had fallen below baseline levels. The analysis of patients' sera showed that at day 2 after mAb infusion, only 50% of the circulating mouse IgG was immunoreactive, and after 1 week, only traces of immunoreactive mouse IgG were detected. All patients developed a human anti-(mouse Ig) response of IgG, IgM and IgA isotypes, although only low levels of anti-idiotypic antibodies were detected at the time of testing (up to 9 weeks) after mAb infusion. No difference in the IgG subclasses of anti-(mouse Ig) antibody was observed between patients treated with mAb and IFNy and patients treated with mAb alone.

Cancer Research, Mar 1, 1987

A monoclonal antibody is described that specifically detects the ganglioside antigens C,mand GD3,... more A monoclonal antibody is described that specifically detects the ganglioside antigens C,mand GD3,binding preferentially to GD2,in melanoma. Antibody specificity was demonstrated with solid-phase radioimmunoassay and enzyme-linked immunosorbent assay as well as by immunostaining on thin-layer chromatography plates using structurally characterized gangliosides. Binding of both the IgG3 antibody and its IgG2a switch variant were assayed on live cells by cytofluorography and by immiumperoxidase staining on frozen tissue sections. The binding patterns cor related with antitumor activity in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays with human effector cells and complement in an '"Ill-release assay using cell lines derived from the same individual. The significant level of killing in all tumor cells tested that express GDI, <M.U or both, suggests the importance of multiple specificity towards tumor antigens, i.e., binding of a monoclonal antibody to two or more tumor-associated antigens.

Cancer Research, Mar 1, 1980

Hybridoma-denived monocbonabanti-coborectal carcinoma antibodies suppressed the growth of coborec... more Hybridoma-denived monocbonabanti-coborectal carcinoma antibodies suppressed the growth of coborectal carcinoma in nude mice as evidenced by a bower incidence of tumors, a longer latency period, and a smaller volume of tumors in antibody-treated than in control animals. The growth-inhibiting properties of monocbonalanti-colomectabantibodies seem to be specific for colorectal carcinoma cells. This is indicated by the lack of effect of the antibodies on the growth of mebanomason bronchogenic carcinomas and by the binding of the antibodies in vivo to coborectal carcinoma cells but not to lung on kidney cells from tumor-bearing animals or to other tumor cells im planted in other animals. Inhibition of tumor growth was most probably mediated by antibody-dependent cell-mediated cy totoxicity. The results of these studies could provide an ap pmoachto the study of immunothemapeuticpossibilities for anti colomectalcarcinoma antibodies in humans. 15. Witz, I., Yagi, Y., and Pressman, D. lgG associated with microsomes from autochthonous hepatomas and normal liver of rats. Cancer Res., 2 7: 2295â€"