immunology by Franz Klaus Jansen
Ricin A-chain cytotoxicity depends on its presentation to the cell membrane
Bioconjugate Chemistry, 1993
Anti-ricin-A-chain monoclonal antibodies (mAbs) were raised in order to study epitopes of the A-c... more Anti-ricin-A-chain monoclonal antibodies (mAbs) were raised in order to study epitopes of the A-chain involved in the initiation of its transmembrane passage. Five nonoverlapping epitopes were selected by cluster formation using a cross-inhibition assay of mAbs from 172 specific hybridomas. For each cluster, representative high affinity mAbs were selected. These mAbs were disulfide-linked to F(ab')2 fragments of a mAb directed against the CD5 antigen. The cytotoxicity of ricin A-chain bound by affinity through different epitopes to these hybrid mAbs was explored on the CD5-positive CEM cells. Without any enhancer, the hybrids displayed cytotoxicity varying in IC50 within a range of 1-10; in the presence of the enhancer NH4Cl, this variation of activity was maintained ranging from 1 to 20; with the enhancer monensin, the variation of cytotoxicity of hybrids extended over a 1-80-fold range. These differences of cytotoxicity were not correlated with mAb properties such as the inhibition of A-chain enzymatic activity, the A-chain binding affinity, the capacity for releasing A-chain at low pH, or the capacity of hybrids for delivering A-chain on the cell surface. This lack of correlation strongly suggests that the different presentations of A-chain epitopes to the cell membrane may be the essential reason for cytotoxicity variations.
Virus induced diabetes and the immune system
Diabetologia, 1977
ABSTRACT
Tolerance to high and low doses of natural crystalline insulin
Diabetologia, 1971
ABSTRACT
Immune reactions to fractions of crystalline insulin
Diabetologia, 1973
ABSTRACT
Diabetologia, 1973
By coupling purified horseradish peroxidase with glutaraldehyde and subsequent reaction with insu... more By coupling purified horseradish peroxidase with glutaraldehyde and subsequent reaction with insulin, conjugates were obtained. These were partially purified by ion exchange chromatography on DEAE-cellulose. A fraction with an average molar ratio of peroxidase to insulin t :0.37 was analysed by electrophoresis and gel filtration. The peroxidase activity of this fraction was found to be 19% of normal and the immunological reactivity 0.6o as compared with that ef insulin.
Tolerance and Immunity to Cristallin Insulin
European Journal of Endocrinology, 1971
Immunotoxins: Hybrid Molecules Combining High Specificity and Potent Cytotoxicity
Immunological Reviews, 1982
... Bernard Pau,; Philippe Poncelet,; Gilbert Richer,; Hubert Vidal,; Guy A. Voisin. Article firs... more ... Bernard Pau,; Philippe Poncelet,; Gilbert Richer,; Hubert Vidal,; Guy A. Voisin. Article first published online: 28 APR 2006. DOI: 10.1111/j.1600-065X.1982.tb00394.x. Issue. Immunological Reviews. Volume 62, Issue 1, pages 185216, February 1982. Additional Information. ...
High specific cytotoxicity of antibody-toxin hybrid molecules (immunotoxins) for target cells
Immunology Letters, 1980
... Press HIGH SPECIFIC CYTOTOXICITY OF ANTIBODY-TOXIN HYBRID MOLECULES (IMMUNOTOXINS) FOR TARGET... more ... Press HIGH SPECIFIC CYTOTOXICITY OF ANTIBODY-TOXIN HYBRID MOLECULES (IMMUNOTOXINS) FOR TARGET CELLS FK JANSENi, Hildur E. BLYTHMANi, D ... After cleavage of the disulphide bridge with 2-mercaptoethanol, the A-chain was isolated on DEAE-Sepharose ...
International Journal of Cancer, 1985
Two ricins were purified from the seeds of Ricinus communis by a simple method based on affinity ... more Two ricins were purified from the seeds of Ricinus communis by a simple method based on affinity chromatography allowing large-scale preparations. Separation of these 2 ricins was achieved by ion-exchange chromatography and studies of purified subunits demonstrated that the 2 forms of ricin differed only in their B-chains which showed widely differing isoelectric points. The Athains isolated from both ricins showed similar biological properties and contained 2 variants, A1 and A2, differing in their molecular weights and carbohydrate contents. These variants could be separated by affinity chromatography on Con-A-Sepharose which bound the A2 variant more tightly than Al. This property allowed us to obtain immunotoxin preparations devoid of free antibodies and to study the in vitro influence of free antibody on immunotoxin activity.
International Journal of Cancer, 1982
Conjugates (immunotoxins) comprising rich A-chain and monoclonal antibody 96.5, which is specific... more Conjugates (immunotoxins) comprising rich A-chain and monoclonal antibody 96.5, which is specific for human melanoma-wociated antigen p97, inhibited protein synthesis and colony formation of cultured human melanoma cells that expressed more than 80,OOO molecules of p97 per cell. Cells expressing fewer than 5,000 molecules of p97 were not killed. The presence of 10 mM ammonium chloride significantly increased the efficiency of the immunotoxin, tumor cells expressing high levels of p97 being killed at immunotoxin concentrations as low as lo-'' M.
Journal of Immunological Methods, 1985
The preparation of lmmunotoxms, hybrid proteins formed by dxsulfide bonding an antibody and the A... more The preparation of lmmunotoxms, hybrid proteins formed by dxsulfide bonding an antibody and the A-chain of ncm, has been studied m detail Optxmal condxtlons, both for the modfflcatxon of the anubody and the couphng reaction between the modified antlbodxes and the toxin subumt, have been deterrmned Con&tlons of time. temperature and stolchlometry stu&ed suggested 2 protocols for each of the 2 steps of thxs preparation Purification and analysxs of the physlcochemlcal and blochermcal properties of the products yielded well-characterized agents, hkely to be of value m chnlcal studxes
Passive Transfer of Lymphocytes from Diabetic Man to Athymic Mouse
The Lancet, 1979
... Marseille, France. d Clinique des Maladies Métaboliques et Endocriniennes, Hôpital St Eloi, M... more ... Marseille, France. d Clinique des Maladies Métaboliques et Endocriniennes, Hôpital St Eloi, Montpellier, France. e Department of Surgery, Ciudad Sanitaria "Principes de Espana", Hospitalet de Llobregat, Barcelona, Spain. f ...
Transplantation Immunity : Localization in Mouse Serum of Antibodies Responsible for Haemagglutination, Cytotoxicity and Enhancement
Nature, 1966
Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells
Nature, 1981
Several attempts to attack tumours in experimental systems have been made using conjugates of che... more Several attempts to attack tumours in experimental systems have been made using conjugates of chemotherapeutic agents or potent toxins with antibodies (immunotoxins). In vitro studies have been highly successful, showing target specificity of a high order in some cases. However, so far, such conjugates have been inadequate in vivo, probably for two main reasons. First, conventional heteroclonal antibodies are perhaps inappropriate, because purification by biochemical methods leaves a large amount of non-antibody gamma-globulins. The use of monoclonal antibodies may overcome this problem. Second, when whole toxins have been conjugated to antibodies there has been a strong residual nonspecific cytotoxicity due to the binding capacity of a subunit, the B-piece of the toxin. (Diphtheria toxin or ricin consist of two polypeptide subunits. The A-piece is responsible for inhibition of protein synthesis on ribosomes, and the B-piece binds to galactose residues on the cell membrane and facilitates the transmembrane passage of the A-piece.) In the present work the problem of nonspecific binding by the B-piece has been circumvented by using the A-piece only as the toxin component of immunotoxins; these immunotoxins are active both in vitro and in vivo.
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immunology by Franz Klaus Jansen