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Biochemical, cytotoxic and pharmacokinetic properties of an immunotoxin composed of a mouse monoclonal antibody Fib75 and the ribosome-inactivating protein alpha-sarcin from Aspergillus giganteus. 1991

E J Wawrzynczak, and R V Henry, and A J Cumber, and G D Parnell, and E J Derbyshire, and N Ulbrich
Institute of Cancer Research, Sutton, England.

An immunotoxin was synthesized by the attachment of alpha-sarcin, the ribosome-inactivating protein derived from the mould Aspergillus giganteus, to a monoclonal mouse IgG2 antibody Fib75. The alpha-sarcin immunotoxin exerted toxic effects in tissue culture against the EJ human bladder carcinoma cell line, expressing the antigen recognised by the Fib75 antibody, inhibiting the incorporation of [3H]leucine by 50% at a concentration of 0.46 nM. The cytotoxic effects of the alpha-sarcin immunotoxin were indistinguishable from those of a Fib75 immunotoxin made with ricin A chain. Fib75-alpha-sarcin was cleared from the circulation of the rat with biphasic kinetics following intravenous administration. The alpha- and beta-phase half-lives were 0.8 h and 6 h, respectively, similar to the serum half-lives of analogous Fib75 immunotoxins made with ribosome-inactivating proteins derived from plants. alpha-Sarcin was completely stable in physiological saline buffer at 37 degrees C, whereas the ribosome-inactivating activity of ricin A chain was gradually lost under identical conditions. alpha-Sarcin may be a valuable alternative to ricin A chain for the construction of therapeutic immunotoxins because of its smaller size and greater thermostability.

UI MeSH Term Description Entries
D011500 Protein Synthesis Inhibitors Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. Protein Synthesis Antagonist,Protein Synthesis Antagonists,Protein Synthesis Inhibitor,Antagonist, Protein Synthesis,Antagonists, Protein Synthesis,Inhibitor, Protein Synthesis,Inhibitors, Protein Synthesis,Synthesis Antagonist, Protein,Synthesis Inhibitor, Protein
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004722 Endoribonucleases A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-. Endoribonuclease
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000922 Immunotoxins Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. Affinotoxin,Antibody-Toxin Conjugate,Antibody-Toxin Conjugates,Antibody-Toxin Hybrid,Antibody-Toxin Hybrids,Chimeric Toxins,Cytotoxin-Antibody Conjugate,Cytotoxin-Antibody Conjugates,Monoclonal Antibody-Toxin Conjugate,Targeted Toxin,Targeted Toxins,Toxin Carriers,Toxin Conjugates,Toxin-Antibody Conjugate,Toxin-Antibody Conjugates,Toxin-Antibody Hybrid,Toxin-Antibody Hybrids,Toxins, Chimeric,Toxins, Targeted,Affinotoxins,Chimeric Toxin,Immunotoxin,Monoclonal Antibody-Toxin Conjugates,Toxin Carrier,Toxin Conjugate,Antibody Toxin Conjugate,Antibody Toxin Conjugates,Antibody Toxin Hybrid,Antibody Toxin Hybrids,Antibody-Toxin Conjugate, Monoclonal,Antibody-Toxin Conjugates, Monoclonal,Carrier, Toxin,Carriers, Toxin,Conjugate, Antibody-Toxin,Conjugate, Cytotoxin-Antibody,Conjugate, Monoclonal Antibody-Toxin,Conjugate, Toxin,Conjugate, Toxin-Antibody,Conjugates, Antibody-Toxin,Conjugates, Cytotoxin-Antibody,Conjugates, Monoclonal Antibody-Toxin,Conjugates, Toxin,Conjugates, Toxin-Antibody,Cytotoxin Antibody Conjugate,Cytotoxin Antibody Conjugates,Hybrid, Antibody-Toxin,Hybrid, Toxin-Antibody,Hybrids, Antibody-Toxin,Hybrids, Toxin-Antibody,Monoclonal Antibody Toxin Conjugate,Monoclonal Antibody Toxin Conjugates,Toxin Antibody Conjugate,Toxin Antibody Conjugates,Toxin Antibody Hybrid,Toxin Antibody Hybrids,Toxin, Chimeric,Toxin, Targeted
D001230 Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae.
D012270 Ribosomes Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION. Ribosome

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