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An immunotoxin (IT) comprising abrin A chain attached to the mouse monoclonal antibody SWA11, recognising a cell surface antigen highly associated with human small cell lung cancer (SCLC), was synthesised using a hindered disulphide crosslinker, N-succinimidyl 3-(2-pyridyldithio) butyrate (SPDB),
The A-chain of the plant toxin abrin was covalently linked to monoclonal anti-Thy 1.1 antibody (OX7) with the use of either N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) or 2-iminothiolane hydrochloride (2IT). The SPDP reagent generates a linkage containing a disulfide bond and an amide bond,
With the object of generating specific cytotoxic agents, we have prepared covalent conjugates of the A-chains of ricin and of abrin with monoclonal antibody LICR-LOND-Fib 75 and investigated their toxicity toward a human tumor cell line in culture. Both conjugates proved to be potent cytotoxins
The coding sequence of abrin-a A-chain (ABRaA) gene was obtained by RT-PCR and cloned into the expression vector pET28b. The mature ABRaA has been highly expressed in the cytoplasm of Escherichia coli by 1 mmol/L IPTG induction, and the yield of the soluble recombinant protein was 4 mg/L of induced
New treatments to overcome the obstacles of conventional anti-cancer therapy are a permanent subject of investigation. One promising approach is the application of toxins linked to cell-specific ligands, so-called immunotoxins. Another attractive option is the employment of toxin-encoding plasmids.
The therapeutic value of antibody-ricin A-chain conjugates (immunotoxins) as antineoplastic agents is limited by their rapid removal from the circulation, primarily by cells of the liver which take up the immunotoxin through receptor mediated recognition of mannose-containing oligosaccharides in the
Two toxic proteins were purified from the seeds of Abrus precatorius by DEAE-A 50 and Sepharose 4B chromatography. One of them does not bind on the Sepharose 4B column (Abrin-b) and the other (Abrin-a) is eluted with 0.2 M galactose. The amino acid compositions and tryptic maps of these two proteins
Abrin, a galactose specific lectin was purified using sepharose 4B affinity column from seeds of Abrus precatorius. It exhibited antitumour activity in mice when used at a sublethal dose of 7.5 micrograms/kg every alternate day for 10 days. Both intralesional and intraperiloneal (i.p.)
The four isoabrins were shown to be capable of inhibiting the growth of tumor cells in vivo when one-fifth of their median lethal dose was used. From the in vitro experiments, the doses required for 50% inhibition of protein biosynthesis are 3.2 pg, 45 ng, 32 ng, and 10 ng/ml for abrin-a, -b, -3,
It has been known that VEGF(121) isoform can serve as a carrier of therapeutic agents targeting tumor endothelial cells. We designed and constructed synthetic cDNA that encodes a chimeric protein comprising abrin-a (ABRaA) toxin A-chain and human VEGF(121). Expression of the ABRaA-VEGF(121) chimeric
Studies on the structures and binding properties of the glycoproteins, purified from human ovarian cyst fluids, will aid the understanding of the carbohydrate alterations occurring during the biosynthesis of blood group antigens and neoplasm formation. These glycoproteins can also serve as important
BACKGROUND
Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer treatment. The toxin
Aqueous extracts of mistletoe (Viscum album L.) contain toxic proteins (lectins) MLI (viscumin), MLII, and MLIII. We previously cloned the gene encoding MLIII precursor. In the present study, a gene fragment encoding the carbohydrate-binding subunit of mistletoe toxic lectin MLIII was cloned and
The seeds of the plant Trichosanthes anguina contain a type I ribosome-inactivating protein (RIP), designated trichoanguin, which was purified to apparent homogeneity by the combined use of ion-exchange chromatographies, i.e. first with DE-52 cellulose and then with CM-52 cellulose. The protein was
Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the