zinostatin and Kidney-Diseases

Neocarzinostatin is a new anticancer drug developed by Japanese investigators. In order to delineate the potential usefulness of this drug, we have reviewed the preclinical data and summarized the Japanese clinical data on 462 patients. The bulk of these patients had carcinoma of the stomach or pancreas and acute leukemia. Neocarzinostatin was administered intravenously in a daily dose of 2-3 mg for five to 15 day periods. Significant antitumor activity was observed in acute leukemia. A few responses were also reported in pancreatic adenocarcinoma, but the drug was inactive against gastric carcinoma. The side effects observed included nausea, vomiting, myelosuppression, fever, and occasional hypersensitivity reactions. The Investigational Drug Branch of the National Cancer Institute has recently sponsored an investigational new drug application with the Food and Drug Administration, and phase I studies are expected to begin soon in the United States.

Topics: Amino Acids; Animals; Antibiotics, Antineoplastic; Cell Division; Chemical Phenomena; Chemistry; Diarrhea; DNA Replication; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Eruptions; Fever; Humans; Hypotension; Kidney Diseases; Leukopenia; Molecular Weight; Nausea; Neoplasms; Neoplasms, Experimental; Temperature; Templates, Genetic; Thrombocytopenia; Zinostatin

-81 and NE-1 idiotypes (Id) of human nephritogenic anti-DNA antibodies are interspecies Id expressed also in NZB/W F1 mice. We tried to manipulate the synthesis of spontaneously occurring anti-DNA antibody using monoclonal anti-Id antibodies (D1E2 and 1F5) conjugated with a cytotoxic agent, neocarzinostatin (NCS). In vivo administration of anti-Id antibodies conjugated with NCS brought about an improvement in the survival rate of female NZB/W F1 mice. It also caused a retardation of development of lupus nephritis and decreased the numbers of anti-DNA-producing cells. The suppression of anti-DNA antibody synthesis was specific and Id-mediated. The results indicate that the use of a limited number of anti-Id antibodies in combination with a cytotoxic agent may be applicable therapeutically to autoimmune diseases.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Anti-Idiotypic; Antibodies, Antinuclear; Autoimmune Diseases; DNA, Single-Stranded; Immunotherapy; Immunotoxins; Kidney Diseases; Kidney Glomerulus; Mice; Mice, Inbred NZB; Proteinuria; Spleen; Zinostatin