Activation of production of infectious tumor virus SV40 in heterokaryon cultures.
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Biomedical subjects
Publications and source records attributed to Z Steplewski.
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Using the histochemical method of McManus the authors investigated the glycogen content in neurons in the reticular formation of brain stem in animals subjected to hyperthermia. For comparison certain nuclei outside the reticular formation were tested in the same region. A significant fall in glycogen content of reticular formation neurons was observed in hyperthermic animals. Changes in the neurons outside the reticular formation were negligible.
IgG3 murine MAb BR55-2 is directed against adenocarcinoma associated Y oligosaccharide. Isotype IgG1, IgG2b and IgG2a switch variants of the BR55-2 antibody were compared in antibody dependent-cell mediated cytotoxicity (ADCC) and complement mediated cytotoxicity (CDC) assays in the murine system. IgG3, IgG2a and IgG2b isotypes mediated ADCC with murine macrophages. Murine splenocytes mediated low levels of ADCC, with IgG3 and IgG2a being always more effective than IgG1 and IgG2b isotypes. All four isotypes were ineffective in CDC with murine serum as a source of complement. In the in vivo experiments, growth of human tumors xenotransplanted into nude mice was best inhibited by both IgG3 and IgG2a isotypes while IgG1 protein was the least effective. Thus, IgG3 and IgG2a isotypes are the most efficient proteins for cancer immunotherapy since they mediate the highest tumoricidal activities in vitro and in vivo.
In 1986, a pilot Phase I/II project was initiated using Iodine-125 labeled anti-epidermal growth factor receptor-425 in the treatment of patients with recurrent glioblastoma multiforme of the brain. The monoclonal antibody was administered intra-arterially by the internal carotid arterial system or the vertebral arterial system depending upon the blood supply to the tumor. The treatment program was repeated at intervals for two or three times. Demonstrated was the intense localization of the monoclonal antibody in the brain tumor prior to therapy using Indium-111 labeled anti-epidermal growth factor receptor-425. This localization was demonstrated prior to any therapy as well as after failure from primary radiation therapy with or without concomitant chemotherapy. To date, 15 patients have been treated following recurrence of their glioma (1/15 metastatic adenocarcinoma) with the monoclonal antibody labeled with Iodine-125. Of the 15 patients, there has been one surgically documented complete response, two partial responders, and five patients with stable disease. The results indicate the potential activity of this radiolabeled monoclonal antibody and have prompted continued accession of patients into a Phase II study as a part of the primary treatment regimen (surgery, radiation therapy with or without chemotherapy) followed by administration of the Iodine-125 labeled anti-epidermal growth factor receptor-425.
The effect of murine anti-canine lymphoma monoclonal antibodies (MAbs) on tumor cell lysis by thioglycolate activated murine macrophages in vitro and tumor growth inhibition in athymic mice was studied. All IgG1 and IgG2a MAbs tested were able to promote specific destruction of canine lymphoma 17-71 cell line by activated macrophages. A correlation between higher ADCC activity and MAb isotype was not clearly evident. In vivo IgG2a and IgG1 MAbs inhibited the growth of canine lymphoma. These results suggest that MAbs of IgG type have potential in immunotherapy of dogs with lymphoma since they have high tumoricidal activity in vivo.