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Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use

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Toxic Plant Proteins

Part of the book series: Plant Cell Monographs ((CELLMONO,volume 18))

Abstract

A number of plant proteins inhibit protein synthesis by irreversibly inactivating the 60S ribosomal subunit in a catalytical, that is, enzymatic, manner. For this property, they are called ribosome-inactivating proteins (RIPs). Several RIPs are utilized in the preparation of therapeutic heteroconjugates (immunotoxins), obtained either by chemical conjugation of a vehicle molecule to an RIP or by genetic fusion of a targeting molecule and an RIP. In the present review, we will focus on the properties of RIPs and of their immunotoxins. The most recent advancements in this domain will be reported in the following paragraphs.

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References

  • Aceto S, Maro D, Conforto B, Siniscalco GG, Parente A, Delli Bovi P, Gaudio L (2005) Nicking activity on pBR322 DNA of ribosome inactivating proteins from Phytolacca dioica L. leaves. Biol Chem 386:307–317

    Article  PubMed  CAS  Google Scholar 

  • Akiyama S, Gottesman MM, Hanover JA, Fitzgerald DJ, Willingham MC, Pastan I (1984) Verapamil enhances the toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin and antitransferrin receptor with Pseudomonas exotoxin. J Cell Physiol 120:271–279

    Article  PubMed  CAS  Google Scholar 

  • Alvarnas JC, Forman SJ (2004) Graft purging in autologous bone marrow transplantation: a promise not quite fulfilled. Oncology (Williston Park) 18:867–876

    Google Scholar 

  • Amlot PL, Stone MJ, Cunningham D, Fay J, Newman J, Collins R, May R, McCarthy M, Richardson J, Ghetie V, Ramilo O, Thorpe PE, Uhr JW, Vitetta ES (1993) A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 82:2624–2633

    PubMed  CAS  Google Scholar 

  • Anonymous (1976) The Second Laboratory SIEB. Studies on the mechanism of abortion induction by trichosanthin. Sci Sin 19(6):811–830

    Google Scholar 

  • Baluna R, Rizo J, Gordon BE, Ghetie V, Vitetta ES (1999) Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. Proc Natl Acad Sci USA 96:3957–3962

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Gorini P, Valbonesi P, Castiglioni P, Stirpe F (1994) Unexpected activity of saporins. Nature 372:624

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Valbonesi P, Bonora E, Gorini P, Bolognesi A, Stirpe F (1997) Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins: effect on DNA, RNA and poly(A). Nucleic Acids Res 25:518–522

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Valbonesi P, Bondioli M, Alvarez ML, Dal MP, Landini MP, Stirpe F (2001) Adenine glycosylase activity in mammalian tissues: an equivalent of ribosome-inactivating proteins. FEBS Lett 505:196–197

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Brigotti M, Perocco P, Carnicelli D, Ciani M, Mercatali L, Stirpe F (2003) Ribosome-inactivating proteins depurinate poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase and have transforming activity for 3T3 fibroblasts. FEBS Lett 538:178–182

    Article  PubMed  CAS  Google Scholar 

  • Barbieri L, Polito L, Bolognesi A, Ciani, M, Pelosi E, Farini V, Jha A, Sharma N, Vivanc, JM, Chambery A, Parente A, Stirpe F (2006) Ribosome-inactivating proteins in edible plants and purification and characterization of a new ribosome-inactivating protein from Cucurbita moschata. Biochim Biophys Acta 1760:783–792

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG (2004) Cytotoxicity and toxicity to animals and humans of ribosome-inactivating proteins. Mini Rev Med Chem 4:513–521

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG, Montacuti V, Stirpe F (1992) High sensitivity of cultured human trophoblasts to ribosome-inactivating proteins. Exp Cell Res 201:109–112

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG, Polito L, Bolognesi A, Lafleur L, Fradet Y, Stirpe F (1996) Toxicity of ribosome-inactivating proteins-containing immunotoxins to a human bladder carcinoma cell line. Int J Cancer 65:485–490

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG, Stirpe F (1995) Ribosome-inactivating proteins from plants. In: Chessin M, DeBorde D, Zipf A (eds) Antiviral Proteins in Higher Plants (eds.) CRC Press, Boca Raton, pp. 39–64

    Google Scholar 

  • Battelli MG, Citores L, Buonamici L, Ferreras JM, de Benito FM, Stirpe F, Girbes T (1997) Toxicity and cytotoxicity of nigrin b, a two-chain ribosome-inactivating protein from Sambucus nigra: comparison with ricin. Arch Toxicol 71:360–364

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG, Bolognesi A, Olivieri F, Polito L, Stirpe F (1998) Different sensitivity of CD30+ cell lines to Ber-H2/saporin-S6 immunotoxin. J Drug Target 5:181–191

    Article  PubMed  CAS  Google Scholar 

  • Battelli MG, Musiani S, Buonamici L, Santi S, Riccio M, Maraldi NM, Girbés T, Stirpe F (2004) Interaction of volkensin with HeLa cells: binding, uptake, intracellular localization, degradation and exocytosis. Cell Mol Life Sci 61:1975–1984

    Article  PubMed  CAS  Google Scholar 

  • Benatti L, Saccardo MB, Dani M, Nitti G, Sassano M, Lorenzetti R, Lappi DA, Soria M (1989) Nucleotide sequence of cDNA coding for saporin-6, a type-1 ribosome-inactivating protein from Saponaria officinalis. Eur J Biochem 183:465–470

    Article  PubMed  CAS  Google Scholar 

  • Bergamaschi G, Perfetti V, Tonon L, Novella A, Lucotti C, Glennie DM, MJ MG, Cazzola M (1996) Saporin, a ribosome-inactivating protein used to prepare immunotoxins, induces cell death via apoptosis. Br J Haematol 93:789–794

    Article  PubMed  CAS  Google Scholar 

  • Bertholdo-Vargas LR, Martins JN, Bordin D, Salvador M, Schafer AE, Barros NM, Barbieri L, Stirpe F, Carlini CR (2009) Type 1 ribosome-inactivating proteins - entomotoxic, oxidative and genotoxic action on Anticarsia gemmatalis (Hubner) and Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). J Insect Physiol 55:51–58

    Article  PubMed  CAS  Google Scholar 

  • Blakey DC, Watson GJ, Knowles PP, Thorpe PE (1987) Effect of chemical deglycosylation of ricin A chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A chain and anti-Thy 1.1 antibody. Cancer Res 47:947–952

    PubMed  CAS  Google Scholar 

  • Blazar BR, Carroll SF, Vallera DA (1991) Prevention of murine graft-versus-host disease and bone marrow alloengraftment across the major histocompatibility barrier after donor graft preincubation with anti-LFA1 immunotoxin. Blood 78(11):3093–3102

    PubMed  CAS  Google Scholar 

  • Blythman HE, Casellas P, Gros O, Gros P, Jansen FK, Paolucci F, Pau B, Vidal H (1981) Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells. Nature 290:145–146

    Article  PubMed  CAS  Google Scholar 

  • Bourrie BJ, Casellas P, Blythman HE, Jansen FK (1986) Study of the plasma clearance of antibody-ricin-A-chain immunotoxins. Evidence for specific recognition sites on the A chain that mediate rapid clearance of the immunotoxin. Eur J Biochem 155:1–10

    Article  PubMed  CAS  Google Scholar 

  • Bregni M, Lappi DA, Siena S, Formosa A, Villa S, Soria M, Bonadonna G, Gianni AM (1988) Activity of a monoclonal antibody–saporin-6 conjugate against B-lymphoma cells. J Natl Cancer Inst 80:511–517

    Article  PubMed  CAS  Google Scholar 

  • Brigotti M, Alfieri R, Sestili P, Bonelli M, Petronini PG, Guidarelli A, Barbieri L, Stirpe F, Sperti S (2002) Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J 16(3):365–372

    Article  PubMed  CAS  Google Scholar 

  • Büssing A (1996) Induction of apoptosis by the mistletoe lectins: a review on the mechanisms of cytotoxicity mediated by Viscum album L. Apoptosis 1:25–32

    Article  Google Scholar 

  • Byers VS, Rodvien R, Grant K, Durrant LG, Hudson KH, Baldwin RW, Scannon PJ (1989) Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer. Cancer Res 49:6153–6160

    PubMed  CAS  Google Scholar 

  • Byers VS, Levin AS, Malvino A, Waites L, Robins RA, Baldwin RW (1994) A phase II study of effect of addition of trichosanthin to zidovudine in patients with HIV disease and failing antiretroviral agents. AIDS Res Hum Retroviruses 10:413–420

    Article  PubMed  CAS  Google Scholar 

  • Candiani C, Franceschi A, Chignola R, Pasti M, Anselmi C, Benoni G, Tridente G, Colombatti M (1992) Blocking effect of human serum but not of cerebrospinal fluid on ricin A chain immunotoxin potentiation by monensin or carrier protein–monensin conjugates. Cancer Res 52:623–630

    PubMed  CAS  Google Scholar 

  • Carlsson J, Drevin H, Axen R (1978) Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent. Biochem J 173:723–737

    PubMed  CAS  Google Scholar 

  • Carnicelli D, Brigotti M, Montanaro L, Sperti S (1992) Differential requirement of ATP and extra-ribosomal proteins for ribosome inactivation by eight RNA N-glycosidases. Biochem Biophys Res Commun 182:579–582

    Article  PubMed  CAS  Google Scholar 

  • Carrière D, Casellas P, Richer G, Gros P, Jansen FK (1985) Endocytosis of an antibody ricin A-chain conjugate (immuno-A-toxin) adsorbed on colloidal gold. Effects of ammonium chloride and monensin. Exp Cell Res 156:327–340

    PubMed  Google Scholar 

  • Casellas P, Brown JP, Gros O, Gros P, Hellstrom I, Jansen FK, Poncelet P, Roncucci R, Vidal H, Hellstrom KE (1982) Human melanoma cells can be killed in vitro by an immunotoxin specific for melanoma-associated antigen p97. Int J Cancer 30:437–443

    Article  PubMed  CAS  Google Scholar 

  • Casellas P, Bourrie BJ, Gros P, Jansen FK (1984) Kinetics of cytotoxicity induced by immunotoxins. Enhancement by lysosomotropic amines and carboxylic ionophores. J Biol Chem 259:9359–9364

    PubMed  CAS  Google Scholar 

  • Castelletti D, Fracasso G, Righetti S, Tridente G, Schnell R, Engert A, Colombatti M (2004) A dominant linear B-cell epitope of ricin A-chain is the target of a neutralizing antibody response in Hodgkin’s lymphoma patients treated with an anti-CD25 immunotoxin. Clin Exp Immunol 136:365–372

    Article  PubMed  CAS  Google Scholar 

  • Cattel L, Delprino L, Brusa P, Dosio F, Comoglio PM, Prat M (1988) Comparison of blocked and non-blocked ricin-antibody immunotoxins against human gastric carcinoma and colorectal adenocarcinoma cell lines. Cancer Immunol Immunother 27:233–240

    Article  PubMed  CAS  Google Scholar 

  • Chignola R, Anselmi C, Dalla SM, Franceschi A, Fracasso G, Pasti M, Chiesa E, Lord JM, Tridente G, Colombatti M (1995) Self-potentiation of ligand–toxin conjugates containing ricin A chain fused with viral structures. J Biol Chem 270:23345–23351

    Article  PubMed  CAS  Google Scholar 

  • Cizeau J, Grenkow DM, Brown JG, Entwistle J, MacDonald GC (2009) Engineering and biological characterization of VB6-845, an anti-EpCAM immunotoxin containing a T-cell epitope-depleted variant of the plant toxin bouganin. J Immunother 32:574–584

    Article  PubMed  CAS  Google Scholar 

  • Clark DS, Emery JM, Munsell MF (1998) Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial cells: 24 month clinical results. J Cataract Refract Surg 24:1614–1620

    PubMed  CAS  Google Scholar 

  • Colombatti M (2002) Ricin A: structure, function and its clinical applications. Chimeric toxins: mechanisms of action and therapeutic applications. Harwood Academic Publishers GmbH, Switzerland, pp 37–85

    Book  Google Scholar 

  • Colombatti M, Dell'Arciprete L, Chignola R, Tridente G (1990) Carrier protein–monensin conjugates: enhancement of immunotoxin cytotoxicity and potential in tumor treatment. Cancer Res 50:1385–1391

    PubMed  CAS  Google Scholar 

  • Cook JP, Savage PM, Lord JM, Roberts LM (1993) Biologically active interleukin 2-ricin A chain fusion proteins may require intracellular proteolytic cleavage to exhibit a cytotoxic effect. Bioconjug Chem 4:440–447

    Article  PubMed  CAS  Google Scholar 

  • Dore JM, Gras E, Wijdenes J (1997) Expression and activity of a recombinant chimeric protein composed of pokeweed antiviral protein and of human interleukin-2. FEBS Lett 402:50–52

    Article  PubMed  CAS  Google Scholar 

  • Endo Y (1988) Mechanism of action of ricin and related toxins on the inactivation of eukaryotic ribosomes. Cancer Treat Res 37:75–89

    Article  PubMed  CAS  Google Scholar 

  • Engert A, Gottstein C, Bohlen H, Winkler U, Schön G, Manske O, Schnell R, Diehl V, Thorpe P (1995) Cocktails of ricin A-chain immunotoxins against different antigens on Hodgkin and Sternberg-Reed cells have superior anti-tumor effects against H-RS cells in vitro and solid Hodgkin tumors in mice. Int J Cancer 63(2):304–309

    Article  PubMed  CAS  Google Scholar 

  • Epstein C, Lynch T, Shefner J, Wen P, Maxted D, Braman V, Ariniello P, Coral F, Ritz J (1994) Use of the immunotoxin N901-blocked ricin in patients with small-cell lung cancer. Int J Cancer Suppl 8:57–59

    Article  PubMed  CAS  Google Scholar 

  • Fabbrini MS, Carpani D, Bello-Rivero I, Soria MR (1997) The amino-terminal fragment of human urokinase directs a recombinant chimeric toxin to target cells: internalization is toxin mediated. FASEB J 11:1169–1176

    PubMed  CAS  Google Scholar 

  • Falini B, Bolognesi A, Flenghi L, Tazzari PL, Broe MK, Stein H, Dürkop H, Aversa F, Corneli P, Pizzolo G, Barbabietola G, Sabattini E, Pileri S, Martelli MF, Stirpe F (1992) Response of refractory Hodgkin’s disease to monoclonal anti-CD30 immunotoxin. Lancet 339:1195–1196

    Article  PubMed  CAS  Google Scholar 

  • Ferreras JM, Barbieri L, Girbés T, Battelli MG, Rojo MA, Arias FJ, Rocher MA, Soriano F, Mendéz E, Stirpe F (1993) Distribution and properties of major ribosome-inactivating proteins (28S rRNA N-glycosidases) of the plant Saponaria officinalis L. (Caryophyllaceae). Biochim Biophys Acta 1216:31–42

    Article  PubMed  CAS  Google Scholar 

  • Fidias P, Grossbard M, Lynch TJ Jr (2002) A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer. Clin Lung Cancer 3:219–222

    Article  PubMed  Google Scholar 

  • Fitzgerald DJ, Trowbridge IS, Pastan I, Willingham MC (1983) Enhancement of toxicity of antitransferrin receptor antibody–Pseudomonas exotoxin conjugates by adenovirus. Proc Natl Acad Sci USA 80:4134–4138

    Article  PubMed  CAS  Google Scholar 

  • Flavell DJ, Boehm DA, Noss A, Warnes SL, Flavell SU (2001) Therapy of human T-cell acute lymphoblastic leukaemia with a combination of anti-CD7 and anti-CD38-SAPORIN immunotoxins is significantly better than therapy with each individual immunotoxin. Br J Cancer 84:571–578

    Article  PubMed  CAS  Google Scholar 

  • Francisco JA, Gawlak SL, Siegall CB (1997) Construction, expression, and characterization of BD1-G28-5 sFv, a single-chain anti-CD40 immunotoxin containing the ribosome-inactivating protein bryodin 1. J Biol Chem 272:24165–24169

    Article  PubMed  CAS  Google Scholar 

  • Frankel AE, FitzGerald D, Siegall C, Press OW (1996) Advances in immunotoxin biology and therapy: a summary of the fourth international symposium on immunotoxins. Cancer Res 56:926–932

    PubMed  CAS  Google Scholar 

  • Frankel AE, Laver JH, Willingham MC, Burns LJ, Kersey JH, Vallera DA (1997) Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-ricin A chain immunotoxin. Leuk Lymphoma 26(3-4):287–298

    PubMed  CAS  Google Scholar 

  • Frankel AE, Fu T, Burbage C, Chandler J, Willingham MC, Tagge EP (1997) IL2 fused to lectin-deficient ricin is toxic to human leukemia cells expressing the IL2 receptor. Leukemia 11:22–30

    Article  PubMed  CAS  Google Scholar 

  • Fuchs H, Bachran D, Panjideh H, Schellmann N, Weng A, Melzig MF, Sutherland M, Bachran C (2009) Saponins as tool for improved targeted tumor therapies. Curr Drug Targets 10:140–151

    Article  PubMed  CAS  Google Scholar 

  • Fulton RJ, Uhr JW, Vitetta ES (1988) In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. Cancer Res 48:2626–2631

    PubMed  CAS  Google Scholar 

  • Gawlak SL, Neubauer M, Klei HE, Chang CY, Einspahr HM, Siegall CB (1997) Molecular, biological, and preliminary structural analysis of recombinant bryodin 1, a ribosome-inactivating protein from the plant Bryonia dioica. Biochemistry 36:3095–3103

    Article  PubMed  CAS  Google Scholar 

  • Geden SE, Gardner RA, Fabbrini MS, Ohashi M, Phanstiel IO, Teter K (2007) Lipopolyamine treatment increases the efficacy of intoxication with saporin and an anticancer saporin conjugate. FEBS J 274:4825–4836

    Article  PubMed  CAS  Google Scholar 

  • Ghetie V, Vitetta E (1994) Immunotoxins in the therapy of cancer: from bench to clinic. Pharmacol Ther 63:209–234

    Article  PubMed  CAS  Google Scholar 

  • Ghetie MA, Tucker K, Richardson J, Uhr JW, Vitetta ES (1992) The antitumor activity of an anti-CD22 immunotoxin in SCID mice with disseminated Daudi lymphoma is enhanced by either an anti-CD19 antibody or an anti-CD19 immunotoxin. Blood 80:2315–2320

    PubMed  CAS  Google Scholar 

  • Ghetie MA, Tucker K, Richardson J, Uhr JW, Vitetta ES (1994) Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail. Blood 84(3):702–707

    PubMed  CAS  Google Scholar 

  • Girbés T, Citores L, Ferreras JM, Rojo MA, Iglesias R, Muñoz R, Arias FJ, Calonge M, Garcia JR, Méndez E (1993) Isolation and partial characterization of nigrin b, a non-toxic novel type 2 ribosome-inactivating protein from the bark of Sambucus nigra L. Plant Mol Biol 22:1181–1186

    Article  PubMed  Google Scholar 

  • Girbés T, Ferreras JM, Iglesias R, Citores L, De TC, Carbajales ML, Jiménez P, de Benito FM, Muñoz R (1996) Recent advances in the uses and applications of ribosome-inactivating proteins from plants. Cell Mol Biol (Noisy-le-grand) 42:461–471

    Google Scholar 

  • Girbés T, Ferreras JM, Arias FJ, Muñoz R, Iglesias R, Jiménez P, Rojo MA, Arias Y, Perez Y, Benitez J, Sanchez D, Gayoso MJ (2003) Non-toxic type 2 ribosome-inactivating proteins (RIPs) from Sambucus: occurrence, cellular and molecular activities and potential uses. Cell Mol Biol (Noisy-le-grand) 49:537–545

    Google Scholar 

  • Girbés T, Ferreras JM, Arias FJ, Stirpe F (2004) Description, distribution, activity and phylogenetic relationship of ribosome-inactivating proteins in plants, fungi and bacteria. Mini Rev Med Chem 4:461–476

    Article  PubMed  Google Scholar 

  • Goldmacher VS, Blattler WA, Lambert JM, McIntyre G, Stewart J (1989) Cytotoxicity of gelonin conjugated to targeting molecules: effects of weak amines, monensin, adenovirus, and adenoviral capsid proteins penton, hexon, and fiber. Mol Pharmacol 36:818–822

    PubMed  CAS  Google Scholar 

  • Gonzalez R, Salem P, Bunn PA Jr, Zukiwski AA, Lamb R, Benjamin RS, Spitler L, Wedel N, Robinson WA (1991) Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial. Mol Biother 3:192–196

    PubMed  CAS  Google Scholar 

  • Gould BJ, Borowitz MJ, Groves ES, Carter PW, Anthony D, Weiner LM, Frankel AE (1989) Phase I study of an anti-breast cancer immunotoxin by continuous infusion: report of a targeted toxic effect not predicted by animal studies. J Natl Cancer Inst 81:775–781

    Article  PubMed  CAS  Google Scholar 

  • Graham ML (2003) Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev 55:1293–1302

    Article  PubMed  CAS  Google Scholar 

  • Griffin TW, Childs LR, FitzGerald DJ, Levine LV (1987) Enhancement of the cytotoxic effect of anti-carcinoembrionic antigen immunotoxins by adenovirus and carboxylic ionophores. J Natl Cancer Inst 79:679–685

    PubMed  CAS  Google Scholar 

  • Griffin T, Rybak ME, Recht L, Singh M, Salimi A, Raso V (1993) Potentiation of antitumor immunotoxins by liposomal monensin. J Natl Cancer Inst 85:292–298

    Article  PubMed  CAS  Google Scholar 

  • Griffiths GD, Leek MD, Gee DJ (1987) The toxic plant proteins ricin and abrin induce apoptotic changes in mammalian lymphoid tissues and intestine. J Pathol 151:221–229

    Article  PubMed  CAS  Google Scholar 

  • Grossbard ML, Fidias P, Kinsella J, O'Toole J, Lambert JM, Blättler WA, Esseltine D, Braman G, Nadler LM, Anderson KC (1998) Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma. Br J Haematol 102:509–515

    Article  PubMed  CAS  Google Scholar 

  • Grossbard ML, Multani PS, Freedman AS, O'Day S, Gribben JG, Rhuda C, Neuberg D, Nadler LM (1999) A phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin’s lymphoma. Clin Cancer Res 5:2392–2398

    PubMed  CAS  Google Scholar 

  • Hartley MR, Lord JM (2004) Cytotoxic ribosome-inactivating lectins from plants. Biochim Biophys Acta 1701:1–14

    Article  PubMed  CAS  Google Scholar 

  • He WJ, Liu WY (2003) Cinnamomum: a multifunctional type II ribosome-inactivating protein. Int J Biochem Cell Biol 35:1021–1027

    Article  PubMed  CAS  Google Scholar 

  • He YW, Guo CX, Pan YF, Peng C, Weng ZH (2008) Inhibition of hepatitis B virus replication by pokeweed antiviral protein in vitro. World J Gastroenterol 14:1592–1597

    Article  PubMed  CAS  Google Scholar 

  • Heisler I, Sutherland M, Bachran C, Hebestreit P, Schnitger A, Melzig MF, Fuchs H (2005) Combined application of saponin and chimeric toxins drastically enhances the targeted cytotoxicity on tumor cells. J Control Release 106:123–137

    Article  PubMed  CAS  Google Scholar 

  • Hertler AA, Schlossman DM, Borowitz MJ, Laurent G, Jansen FK, Schmidt C, Frankel AE (1988) A phase I study of T101-ricin A chain immunotoxin in refractory chronic lymphocytic leukemia. J Biol Response Mod 7:97–113

    PubMed  CAS  Google Scholar 

  • Hertler AA, Schlossman DM, Borowitz MJ, Blythman HE, Casellas P, Frankel AE (1989) An anti-CD5 immunotoxin for chronic lymphocytic leukemia: enhancement of cytotoxicity with human serum albumin–monensin. Int J Cancer 43:215–219

    Article  PubMed  CAS  Google Scholar 

  • Hu R, Zhai Q, Liu W, Liu X (2001) An insight into the mechanism of cytotoxicity of ricin to hepatoma cell: roles of Bcl-2 family proteins, caspases, Ca(2+)-dependent proteases and protein kinase C. J Cell Biochem 81:583–593

    Article  PubMed  CAS  Google Scholar 

  • Hu RG, Zhai QW, He WJ, Mei L, Liu WY (2002) Bioactivities of ricin retained and its immunoreactivity to anti-ricin polyclonal antibodies alleviated through pegylation. Int J Biochem Cell Biol 34:396–402

    Article  PubMed  CAS  Google Scholar 

  • Hudak KA, Bauman JD, Tumer NE (2002) Pokeweed antiviral protein binds to the cap structure of eukaryotic mRNA and depurinates the mRNA downstream of the cap. RNA 8:1148–1159

    Article  PubMed  CAS  Google Scholar 

  • Hughes JN, Lindsay CD, Griffiths GD (1996) Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death. Human Exp Toxicol 15:443–451

    Article  CAS  Google Scholar 

  • Iordanov MS, Pribnow D, Magun JL, Dinh TH, Pearson JA, Chen SL, Magun BE (1997) Ribotoxic stress response: activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol Cell Biol 17:3373–3381

    PubMed  CAS  Google Scholar 

  • Irvin JD (1975) Purification and partial characterization of the antiviral protein from Phytolacca americana which inhibits eukaryotic protein synthesis. Arch Biochem Biophys 169:522–528

    Article  PubMed  CAS  Google Scholar 

  • Jaffrezou JP, Levade T, Kuhlein E, Thurneyssen O, Chiron M, Grandjean H, Carrière D, Laurent G (1990) Enhancement of ricin A chain immunotoxin activity by perhexiline on established and fresh leukemic cells. Cancer Res 50:5558–5566

    PubMed  CAS  Google Scholar 

  • Jaffrezou JP, Levade T, Thurneyssen O, Chiron M, Bordier C, Attal M, Chatelain P, Laurent G (1992) In vitro and in vivo enhancement of ricin-A chain immunotoxin activity by novel indolizine calcium channel blockers: delayed intracellular degradation linked to lipidosis induction. Cancer Res 52:1352–1359

    PubMed  CAS  Google Scholar 

  • Jansen FK, Blythman HE, Carrière D, Casellas P, Gros O, Gros P, Laurent JC, Paolucci F, Pau B, Poncelet P, Richer G, Vidal H, Voisin GA (1982) Immunotoxins: hybrid molecules combining high specificity and potent cytotoxicity. Immunol Rev 62:185–216

    Article  PubMed  CAS  Google Scholar 

  • Jansen FK, Jansen A, Derocq JM, Carrière D, Carayon P, Veas F, Jaffrezou JP (1992) Golgi vacuolization and immunotoxin enhancement by monensin and perhexiline depend on a serum protein. Implications for intracellular trafficking. J Biol Chem 267:12577–12582

    PubMed  CAS  Google Scholar 

  • Kataoka J, Ago H, Habuka N, Furuno M, Masuta C, Miyano M, Koiwai A (1993) Expression of a pokeweed antiviral protein in Escherichia coli and its characterization. FEBS Lett 320:31–34

    Article  PubMed  CAS  Google Scholar 

  • Kreitman RJ (1997) Getting plant toxins to fuse. Leuk Res 21:997–999

    Article  PubMed  CAS  Google Scholar 

  • Krolick KA, Villemez C, Isakson P, Uhr JW, Vitetta ES (1980) Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin. Proc Natl Acad Sci USA 77:5419–5423

    Article  PubMed  CAS  Google Scholar 

  • Lambert JM, Senter PD, Yau-Young A, Blättler WA, Goldmacher VS (1985) Purified immunotoxins that are reactive with human lymphoid cells. Monoclonal antibodies conjugated to the ribosome-inactivating proteins gelonin and the pokeweed antiviral proteins. J Biol Chem 260:12035–12041

    PubMed  CAS  Google Scholar 

  • Lambert JM, McIntyre G, Gauthier MN, Zullo D, Rao V, Steeves RM, Goldmacher VS, Blättler WA (1991) The galactose-binding sites of the cytotoxic lectin ricin can be chemically blocked in high yield with reactive ligands prepared by chemical modification of glycopeptides containing triantennary N-linked oligosaccharides. Biochemistry 30:3234–3247

    Article  PubMed  CAS  Google Scholar 

  • Lappi DA, Wiley RG (2004) Immunotoxins and neuropeptide–toxin conjugates experimental applications. Mini Rev Med Chem 4:585–595

    Article  PubMed  CAS  Google Scholar 

  • Laske DW, Muraszko KM, Oldfield EH, DeVroom HL, Sung C, Dedrick RL, Simon TR, Colandrea J, Copeland C, Katz D, Greenfield L, Groves ES, Houston LL, Youle RJ (1997) Intraventricular immunotoxin therapy for leptomeningeal neoplasia. Neurosurgery 41:1039–1049

    Article  PubMed  CAS  Google Scholar 

  • Legname G, Gromo G, Lord JM, Monzini N, Modena D (1993) Expression and activity of pre-dianthin 30 and dianthin 30. Biochem Biophys Res Commun 192:1230–1237

    Article  PubMed  CAS  Google Scholar 

  • LeMaistre CF, Rosen S, Frankel A, Kornfeld S, Saria E, Meneghetti C, Drajesk J, Fishwild D, Scannon P, Byers V (1991) Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. Blood 78:1173–1182

    PubMed  CAS  Google Scholar 

  • Lin JY, Liu K, Chen CC, Tung TC (1971) Effect of crystalline ricin on the biosynthesis of protein, RNA, and DNA in experimental tumor cells. Cancer Res 31:921–924

    PubMed  CAS  Google Scholar 

  • Lizzi AR, D'Alessandro AM, Zeolla N, Brisdelli F, D'Andrea G, Pitari G, Oratore A, Bozzi A, Ippoliti R (2005) The effect of AZT and chloroquine on the activities of ricin and a saporin-transferrin chimeric toxin. Biochem Pharmacol 70:560–569

    Article  PubMed  CAS  Google Scholar 

  • Lord JM, Deeks E, Marsden CJ, Moore K, Pateman C, Smith C, Spooner RA, Watson P, Roberts LM (2003) Retrograde transport of toxins across the endoplasmic reticulum membrane. Biochem Soc Trans 31:1260–1262

    Article  PubMed  CAS  Google Scholar 

  • Lorenzetti I, Meneguzzi A, Fracasso G, Potrich C, Costantini L, Chiesa E, Legname G, Menestrina G, Tridente G, Colombatti M (2000) Genetic grafting of membrane-acting peptides to the cytotoxin dianthin augments its ability to de-stabilize lipid bilayers and enhances its cytotoxic potential as the component of transferrin–toxin conjugates. Int J Cancer 86:582–589

    Article  PubMed  CAS  Google Scholar 

  • LoRusso PM, Lomen PL, Redman BG, Poplin E, Bander JJ, Valdivieso M (1995) Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. Am J Clin Oncol 18:307–312

    Article  PubMed  CAS  Google Scholar 

  • Mabley JG, Pacher P, Szabo C (2009) Activation of the cholinergic anti-inflammatory pathway reduces ricin-induced mortality and organ failure in mice. Mol Med 15:166–172

    Article  PubMed  CAS  Google Scholar 

  • McGrath MS, Hwang KM, Caldwell SE, Gaston I, Luk KC, Wu P, Ng VL, Crowe S, Daniels J, Marsh J (1989) GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage. Proc Natl Acad Sci USA 86:2844–2848

    Article  PubMed  CAS  Google Scholar 

  • McIntosh DP, Edwards DC, Cumber AJ, Parnell GD, Dean CJ, Ross WC, Forrester JA (1983) Ricin B chain converts a non-cytotoxic antibody–ricin A chain conjugate into a potent and specific cytotoxic agent. FEBS Lett 164:17–20

    Article  PubMed  CAS  Google Scholar 

  • Messmann RA, Vitetta ES, Headlee D, Senderowicz AM, Figg WD, Schindler J, Michiel DF, Creekmore S, Steinberg SM, Kohler D, Jaffe ES, Stetler-Stevenson M, Chen H, Ghetie V, Sausville EA (2000) A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma. Clin Cancer Res 6:1302–1313

    PubMed  CAS  Google Scholar 

  • Mollenhauer HH, Morre DJ, Rowe LD (1990) Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim Biophys Acta 1031:225–246

    Article  PubMed  CAS  Google Scholar 

  • Monti B, D'Alessandro C, Farini V, Bolognesi A, Polazzi E, Contestabile A, Stirpe F, Battelli MG (2007) In vitro and in vivo toxicity of type 2 ribosome-inactivating proteins lanceolin and stenodactylin on glial and neuronal cells. Neurotoxicology 28:637–644

    Article  PubMed  CAS  Google Scholar 

  • Narayanan S, Surolia A, Karande AA (2004) Ribosome inactivating protein and apoptosis: abrin causes cell death via mitochondrial pathway in Jurkat cells. Biochem J 377:233–240

    Article  PubMed  CAS  Google Scholar 

  • Ng TB (2004) Antifungal proteins and peptides of leguminous and non-leguminous origins. Peptides 25:1215–1222

    Article  PubMed  CAS  Google Scholar 

  • Ng TB, Chan WY, Yeung HW (1992) Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor and anti-AIDS activities from Cucurbitaceae plants. Gen Pharmacol 23:579–590

    PubMed  CAS  Google Scholar 

  • Nicolas E, Beggs JM, Haltiwanger BM, Taraschi TF (1998) A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA. J Biol Chem 273:17216–17220

    Article  PubMed  CAS  Google Scholar 

  • Nolan PA, Garrison DA, Better M (1993) Cloning and expression of a gene encoding gelonin, a ribosome-inactivating protein from Gelonium multiflorum. Gene 134:223–227

    Article  PubMed  CAS  Google Scholar 

  • Obrig TG (1997) Shiga toxin mode of action in E. coli O157:H7 disease. Front Biosci 2:d635–d642

    PubMed  CAS  Google Scholar 

  • O'Hare M, Roberts LM, Thorpe PE, Watson GJ, Prior B, Lord JM (1987) Expression of ricin A chain in Escherichia coli. FEBS Lett 216:73–78

    Article  PubMed  Google Scholar 

  • Olsen NJ, Brooks RH, Cush JJ, Lipsky PE, St Clair EW, Matteson EL, Gold KN, Cannon GW, Jackson CG, McCune WJ, Fox DA, Nelson B, Lorenz T, Strand V (1996) A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. The Xoma RA Investigator Group. Arthritis Rheum 39:1102–1108

    Article  PubMed  CAS  Google Scholar 

  • Olsnes S, Pihl A (1972) Ricin – a potent inhibitor of protein synthesis. FEBS Lett 20:327–329

    Article  PubMed  CAS  Google Scholar 

  • Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ (2007) Immunotoxin treatment of cancer. Annu Rev Med 58:221–237

    Article  PubMed  CAS  Google Scholar 

  • Pelosi E, Lubelli C, Polito L, Barbieri L, Bolognesi A, Stirpe F (2005) Ribosome-inactivating proteins and other lectins from Adenia (Passifloraceae). Toxicon 46:658–663

    Article  PubMed  CAS  Google Scholar 

  • Peumans WJ, Hao Q, Van Damme EJ (2001) Ribosome-inactivating proteins from plants: more than RNA N-glycosidases? FASEB J 15:1493–1506

    Article  PubMed  CAS  Google Scholar 

  • Poole B, Ohkuma S (1981) Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol 90:665–669

    Article  PubMed  CAS  Google Scholar 

  • Ralston HJ III (2005) Pain and the primate thalamus. Prog Brain Res 149:1–10

    Article  PubMed  Google Scholar 

  • Ramakrishnan S, Houston LL (1984) Inhibition of human acute lymphoblastic leukemia cells by immunotoxins: potentiation by chloroquine. Science 223:58–61

    Article  PubMed  CAS  Google Scholar 

  • Ramakrishnan S, Bjorn MJ, Houston LL (1989) Recombinant ricin A chain conjugated to monoclonal antibodies: improved tumor cell inhibition in the presence of lysosomotropic compounds. Cancer Res 49:613–617

    PubMed  CAS  Google Scholar 

  • Raso V, Lawrence J (1984) Carboxylic ionophores enhance the cytotoxic potency of ligand- and antibody-delivered ricin A chain. J Exp Med 160:1234–1240

    Article  PubMed  CAS  Google Scholar 

  • Ravel S, Casellas P (1990) Internalization of the cytotoxic molecules of T101 F(ab′)2-(ricin-A-chain) immunotoxin into human T-leukemic cells. Eur J Biochem 192:469–473

    Article  PubMed  CAS  Google Scholar 

  • Ravel S, Colombatti M, Casellas P (1992) Internalization and intracellular fate of anti-CD5 monoclonal antibody and anti-CD5 ricin A-chain immunotoxin in human leukemic T cells. Blood 79:1511–1517

    PubMed  CAS  Google Scholar 

  • Reddy KR (2004) Development and pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a (40 kD). Semin Liver Dis 24(Suppl 2):33–38

    Article  PubMed  CAS  Google Scholar 

  • Reisbig R, Olsnes S, Eiklid K (1981) The cytotoxic activity of Shigella toxin. Evidence for catalytic inactivation of the 60 S ribosomal subunit. J Biol Chem 256:8739–8744

    PubMed  CAS  Google Scholar 

  • Sandvig K, van Deurs B (2002) Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett 529:49–53

    Article  PubMed  CAS  Google Scholar 

  • Sausville EA, Headlee D, Stetler-Stevenson M, Jaffe ES, Solomon D, Figg WD, Herdt J, Kopp WC, Rager H, Steinberg SM, Ghetie V, Schindler J, Uhr J, Vitetta ES (1995) Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood 85:3457–3465

    PubMed  CAS  Google Scholar 

  • Schnell R, Vitetta E, Schindler J, Barth S, Winkler U, Borchmann P, Hansmann ML, Diehl V, Ghetie V, Engert A (1998) Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin’s lymphoma. Leuk Lymphoma 30:525–537

    PubMed  CAS  Google Scholar 

  • Schnell R, Vitetta E, Schindler J, Borchmann P, Barth S, Ghetie V, Hell K, Drillich S, Diehl V, Engert A (2000) Treatment of refractory Hodgkin’s lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia 14:129–135

    Article  PubMed  CAS  Google Scholar 

  • Schnell R, Staak O, Borchmann P, Schwartz C, Matthey B, Hansen H, Schindler J, Ghetie V, Vitetta ES, Diehl V, Engert A (2002) Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin’s and non-Hodgkin’s lymphoma. Clin Cancer Res 8:1779–1786

    PubMed  CAS  Google Scholar 

  • Schnell R, Borchmann P, Staak JO, Schindler J, Ghetie V, Vitetta ES, Engert A (2003) Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’s lymphoma. Ann Oncol 14:729–736

    Article  PubMed  CAS  Google Scholar 

  • Selvaggi K, Saria EA, Schwartz R, Vlock DR, Ackerman S, Wedel N, Kirkwood JM, Jones H, Ernstoff MS (1993) Pase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma. J Immunother Emphasis Tumor Immunol 13:201–207

    Article  PubMed  CAS  Google Scholar 

  • Shaw PC, Chan WL, Yeung HW, Ng TB (1994) Minireview: trichosanthin – a protein with multiple pharmacological properties. Life Sci 55:253–262

    Article  PubMed  CAS  Google Scholar 

  • Siena S, Villa S, Bregni M, Bonnadonna G, Gianni AM (1987) Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A-chain immunotoxin. Blood 69:345–348

    PubMed  CAS  Google Scholar 

  • Siena S, Bregni M, Formosa A, Martineau D, Lappi DA, Bonadonna G, Gianni AM (1988) Evaluation of antihuman T lymphocyte saporin immunotoxins potentially useful in human transplantation. Transplantation 46:747–753

    Article  PubMed  CAS  Google Scholar 

  • Sikriwal D, Ghosh P, Batra JK (2008) Ribosome inactivating protein saporin induces apoptosis through mitochondrial cascade, independent of translation inhibition. Int J Biochem Cell Biol 40:2880–2888

    Article  PubMed  CAS  Google Scholar 

  • Singh M, Griffin T, Salimi A, Micetich RG, Atwal H (1994) Potentiation of ricin A immunotoxin by monoclonal antibody targeted monensin containing small unilamellar vesicles. Cancer Lett 84:15–21

    Article  PubMed  CAS  Google Scholar 

  • Smallshaw JE, Ghetie V, Rizo J, Fulmer JR, Trahan LL, Ghetie MA, Vitetta ES (2003) Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol 21:387–391

    Article  PubMed  CAS  Google Scholar 

  • Soler-Rodriguez AM, Ghetie MA, Oppenheimer-Marks N, Uhr JW, Vitetta ES (1993) Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implications for vascular leak syndrome. Exp Cell Res 206:227–234

    Article  PubMed  CAS  Google Scholar 

  • Spitler LE, del Rio M, Khentigan A, Wedel NI, Brophy NA, Miller LL, Harkonen WS, Rosendorf LL, Lee HM, Mischak RP (1987) Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res 47:1717–1723

    PubMed  CAS  Google Scholar 

  • Stafford FJ, Fleisher TA, Lee G, Brown M, Strand V, Austin HA III, Balow JE, Klippel JH (1994) A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus. J Rheumatol 21:2068–2070

    PubMed  CAS  Google Scholar 

  • Stirpe F (2004) Ribosome-inactivating proteins. Toxicon 44:371–383

    Article  PubMed  CAS  Google Scholar 

  • Stirpe F, Battelli MG (2006) Ribosome-inactivating proteins: progress and problems. Cell Mol Life Sci 63:1850–1866

    Article  PubMed  CAS  Google Scholar 

  • Stirpe F, Bailey S, Miller SP, Bodley JW (1988) Modification of ribosomal RNA by ribosome-inactivating proteins from plants. Nucleic Acids Res 16:1349–1357

    Article  PubMed  CAS  Google Scholar 

  • Stone MJ, Sausville EA, Fay JW, Headlee D, Collins RH, Figg WD, Stetler-Stevenson M, Jain V, Jaffe ES, Solomon D, Lush RM, Senderowicz A, Ghetie V, Schindler J, Uhr JW, Vitetta ES (1996) A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood 88:1188–1197

    PubMed  CAS  Google Scholar 

  • Strand V, Lipsky PE, Cannon GW, Calabrese LH, Wiesenhutter C, Cohen SB, Olsen NJ, Lee ML, Lorenz TJ, Nelson B (1993) Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group. Arthritis Rheum 36:620–630

    Article  PubMed  CAS  Google Scholar 

  • Suzuki A, Doi H, Matsuzawa F, Aikawa S, Takiguchi K, Kawano H, Hayashida M, Ohno S (2000) Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible association between bcl-2 and tissue failure by E. coli O157:H7. Genes Dev 14:1734–1740

    PubMed  CAS  Google Scholar 

  • Szalai K, Scholl I, Forster-Waldl E, Polito L, Bolognesi A, Untersmayr E, Riemer AB, Boltz-Nitulescu G, Stirpe F, Jensen-Jarolim E (2005) Occupational sensitization to ribosome-inactivating proteins in researchers. Clin Exp Allergy 35:1354–1360

    Article  PubMed  CAS  Google Scholar 

  • Tetzke TA, Caton MC, Maher PA, Parandoosh Z (1997) Effect of fibroblast growth factor saporin mitotoxins on human bladder cell lines. Clin Exp Metastasis 15:620–629

    Article  PubMed  CAS  Google Scholar 

  • Thiesen HJ, Juhl H, Arndt R (1987) Selective killing of human bladder cancer cells by combined treatment with A and B chain ricin antibody conjugates. Cancer Res 47:419–423

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Ross WC, Brown AN, Myers CD, Cumber AJ, Foxwell BM, Forrester JT (1984) Blockade of the galactose-binding sites of ricin by its linkage to antibody. Specific cytotoxic effects of the conjugates. Eur J Biochem 140:63–71

    Article  PubMed  CAS  Google Scholar 

  • Thorpe PE, Wallace PM, Knowles PP, Relf MG, Brown AN, Watson GJ, Knyba RE, Wawrzynczak EJ, Blakey DC (1987) New coupling agents for the synthesis of immunotoxins containing a hindered disulfide bond with improved stability in vivo. Cancer Res 47:5924–5931

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Wallace PM, Knowles PP, Relf MG, Brown AN, Watson GJ, Blakey DC, Newell DR (1988) Improved antitumor effects of immunotoxins prepared with deglycosylated ricin A-chain and hindered disulfide linkages. Cancer Res 48:6396–6403

    PubMed  CAS  Google Scholar 

  • Thorpe SC, Kemeny DM, Panzani R, Lessof MH (1988) Allergy to castor bean. I. Its relationship to sensitization to common inhalant allergens (atopy). J Allergy Clin Immunol 82:62–66

    Article  PubMed  CAS  Google Scholar 

  • Thorpe SC, Murdoch RD, Kemeny DM (1989) The effect of the castor bean toxin, ricin, on rat IgE and IgG responses. Immunology 68:307–311

    PubMed  CAS  Google Scholar 

  • Tolstikov VV, Cole R, Fang H, Pincus SH (1997) Influence of endosome-destabilizing peptides on efficacy of anti-HIV immunotoxins. Bioconjug Chem 8:38–43

    Article  PubMed  CAS  Google Scholar 

  • Tommasi M, Castelletti D, Pasti M, Fracasso G, Lorenzetti I, Sartoris S, Pera C, Ferrara GB, Tridente G, Colombatti M (2001) Identification of ricin A-chain HLA class II-restricted epitopes by human T-cell clones. Clin Exp Immunol 125:391–400

    Article  PubMed  CAS  Google Scholar 

  • Uckun FM (1993) Immunotoxins for the treatment of leukaemia. Br J Haematol 85:435–438

    Article  PubMed  CAS  Google Scholar 

  • Uckun FM, Kersey JH, Vallera DA, Ledbetter JA, Weisdorf D, Myers DE, Haake R, Ramsay NK (1990) Autologous bone marrow transplantation in high-risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. Blood 76:1723–1733

    PubMed  CAS  Google Scholar 

  • Vago R, Marsden CJ, Lord JM, Ippoliti R, Flavell DJ, Flavell SU, Ceriotti A, Fabbrini MS (2005) Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J 272:4983–4995

    Article  PubMed  CAS  Google Scholar 

  • Van Damme EJ, Hao Q, Barre A, Vandenbussche F, Desmyter S, Rougè P, Peumans WJ (2001) Ribosome-inactivating proteins: a family of proteins that do more than inactivate ribosomes. Crit Rev Plant Sci 20:395–465

    Google Scholar 

  • van Horssen PJ, Preijers FW, van Oosterhout YV, de Witte T (1996) Highly potent CD22-recombinant ricin A results in complete cure of disseminated malignant B-cell xenografts in SCID mice but fails to cure solid xenografts in nude mice. Int J Cancer 68:378–383

    Article  PubMed  Google Scholar 

  • van Horssen PJ, van Oosterhout YV, Evers S, Backus HH, van Oijen MG, Bongaerts R, de Witte T, Preijers FW (1999) Influence of cytotoxicity enhancers in combination with human serum on the activity of CD22-recombinant ricin A against B cell lines, chronic and acute lymphocytic leukemia cells. Leukemia 13:241–249

    Article  PubMed  CAS  Google Scholar 

  • Vitetta ES (1986) Synergy between immunotoxins prepared with native ricin A chains and chemically-modified ricin B chains. J Immunol 136:1880–1887

    PubMed  CAS  Google Scholar 

  • Vitetta ES, Cushley W, Uhr JW (1983) Synergy of ricin A chain-containing immunotoxins and ricin B chain-containing immunotoxins in in vitro killing of neoplastic human B cells. Proc Natl Acad Sci USA 80:6332–6335

    Article  PubMed  CAS  Google Scholar 

  • Vitetta ES, Fulton RJ, Uhr JW (1984) Cytotoxicity of a cell-reactive immunotoxin containing ricin A chain is potentiated by an anti-immunotoxin containing ricin B chain. J Exp Med 160:341–346

    Article  PubMed  CAS  Google Scholar 

  • Vitetta ES, Stone M, Amlot P, Fay J, May R, Till M, Newman J, Clark P, Collins R, Cunningham D, Ghetie V, Uhr JW, Thorpe PE (1991) Phase I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 51:4052–4058

    PubMed  CAS  Google Scholar 

  • Vivanco JM, Savary BJ, Flores HE (1999) Characterization of two novel type I ribosome-inactivating proteins from the storage roots of the Andean crop Mirabilis expansa. Plant Physiol 119:1447–1456

    Article  PubMed  CAS  Google Scholar 

  • Waterer GW, Robertson H (2009) Bioterrorism for the respiratory physician. Respirology 14:5–11

    Article  PubMed  Google Scholar 

  • Weiner LM, O’Dwyer J, Kitson J, Comis RL, Frankel AE, Bauer RJ, Konrad MS, Groves ES (1989) Phase I evaluation of an anti-breast carcinoma monoclonal antibody 260F9-recombinant ricin A chain immunoconjugate. Cancer Res 49(14):4062–4067

    PubMed  CAS  Google Scholar 

  • Wiley RG, Lappi DA (2003) Targeted toxins in pain. Adv Drug Deliv Rev 55:1043–1054

    Article  PubMed  CAS  Google Scholar 

  • Wiley RG, Lappi DA (2005) Molecular neurosurgery with targeted toxins. Humana Press Inc, Totowa, NJ

    Book  Google Scholar 

  • Wiley RG, Stirpe F (1988) Modeccin and volkensin but not abrin are effective suicide transport agents in rat CNS. Brain Res 438:145–154

    Article  PubMed  CAS  Google Scholar 

  • Wiley RG, Berbos TG, Deckwerth TL, Johnson EM Jr, Lappi DA (1995) Destruction of the cholinergic basal forebrain using immunotoxin to rat NGF receptor: modeling the cholinergic degeneration of Alzheimer’s disease. J Neurol Sci 128:157–166

    Article  PubMed  CAS  Google Scholar 

  • Wong L, Suh DY, Frankel AE (2005) Toxin conjugate therapy of cancer. Semin Oncol 32:591–595

    Article  PubMed  CAS  Google Scholar 

  • Wood KA, Lord JM, Wawrzynczak EJ, Piatak M (1991) Preproabrin: genomic cloning, characterisation and the expression of the A-chain in Escherichia coli. Eur J Biochem 198:723–732

    Article  PubMed  CAS  Google Scholar 

  • Yeung HW, Li WW, Feng Z, Barbieri L, Stirpe F (1988) Trichosanthin, alpha-momorcharin and beta-momorcharin: identity of abortifacient and ribosome-inactivating proteins. Int J Pept Protein Res 31:265–268

    Article  PubMed  CAS  Google Scholar 

  • Youle RJ, Neville DM Jr (1982) Kinetics of protein synthesis inactivation by ricin-anti Thy 1.1 monoclonal antibody hybrids. Role of the ricin B subunit demonstrated by reconstitution. J Biol Chem 257:1598–1601

    PubMed  CAS  Google Scholar 

  • Youn YS, Na DH, Yoo SD, Song SC, Lee KC (2005) Carbohydrate-specifically polyethylene glycol-modified ricin A-chain with improved therapeutic potential. Int J Biochem Cell Biol 37:1525–1533

    Article  PubMed  CAS  Google Scholar 

  • Yu L, Gu F, Zhang C, Xie S, Guo Y (1998) Targeted diagnosis and treatment of superficial bladder cancer with monoclonal antibody BDI-1. Chin Med J (Engl) 111:404–407

    CAS  Google Scholar 

  • Zang Z, Xu H, Yu L, Yang D, Xie S, Shi Y, Li Z, Li J, Wang J, Li M, Guo Y, Gu F (2000) Intravesical immunotoxin as adjuvant therapy to prevent the recurrence of bladder cancer. Chin Med J (Engl) 113:1002–1006

    CAS  Google Scholar 

  • Zarling JM, Moran PA, Haffar O, Sias J, Richman DD, Spina CA, Myers DE, Kuebelbeck V, Ledbetter JA, Uckun FM (1990) Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies. Nature 347:92–95

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Sun S, Feng D, Zhao WL, Sui SF (2009) A novel strategy for the invasive toxin: hijacking exosome-mediated intercellular trafficking. Traffic 10:411–424

    Article  PubMed  CAS  Google Scholar 

  • Zheng SS, Wai WL, Hin WY, Wu AR (1991) Kinetics of IgE antibody response to trichosanthin α-momorcharin and beta-momorcharin in mice. Chin Med J (Engl) 104:292–299

    CAS  Google Scholar 

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Acknowledgments

The help and advice of Dr. Serena Fabbrini (Istituto di Biologia e Biotecnologia Agraria, CNR, Milano, Italy) are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pathology, University of Verona, Policlinico “G.B. Rossi”, P.le L. Scuro 10, 37134, Verona, Italy

    Giulio Fracasso & Marco Colombatti

  2. Via S. Petronio Vecchio 19, 40125, Bologna, Italy

    Fiorenzo Stirpe

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  1. Giulio Fracasso
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  1. Dept. Biological Sciences, University of Warwick, Coventry, CV47AL, United Kingdom

    J. Michael Lord

  2. Dept. Biological Sciences, University of Warwick, Coventry, CV47AL, United Kingdom

    Martin R. Hartley

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Fracasso, G., Stirpe, F., Colombatti, M. (2010). Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use. In: Lord, J., Hartley, M. (eds) Toxic Plant Proteins. Plant Cell Monographs, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12176-0_12

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