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Clinical Applications of Immunotoxins pp 13–33Cite as

The Emerging Role of Ricin A-Chain Immunotoxins in Leukemia and Lymphoma

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 234))

Abstract

Although some malignancies can be cured by conventional modalities including surgery, radiotherapy and polychemotherapy, many cancer patients still ultimately die of their disease. The major reason for this poor outcome is the persistence or selection of cells which are refractory to conventional treatment. These cells might be eradicated by new immunotherapeutic agents with different modes of action. In this regard, monoclonal antibodies (Moabs) have become available in limitless quantities making more selective immunotherapy feasible. These Moabs can bind to well-defined antigens expressed on the surface of malignant cells. Unfortunately, many Moabs have very weak or no anti-tumor activity when used in their native form. Thus, Moabs are often linked to radioisotopes or toxins to increase their toxicity. Immunotoxins (ITs) are constructed by chemically or genetically linking the antibody moiety to a potent bacterial or plant toxin. To date, the most widely used toxin is ricin, which is derived from the seeds of Ricinus communis (castor bean).

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References

  • Amlot PL, Stone MJ, Cunningham D, Fay J, Newman J, Collins R, May R, McCarthy M, Richardson J, Ghetie V et al (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 

  • Baluna R, Getie V, Oppenhimer-Marks N, Vitetta ES (1995) The binding of ricin A-chain immunotoxin to fibronectin: possible implications for vascular leak syndrome in immunotoxin-treated patients. 4th international symposium on immunotoxins, p 144

    Google Scholar 

  • Baluna R, Sausville EA, Stone MJ, Stetler-Stevenson MA, Uhr J, Vitetta ES (1996) Decreases in levels of serum fibronectin predict the severity of vascular leak syndrome in patients treated with ricin A-chaincontaining immunotoxins. Clin Cancer Res 2: 1705–1712

    PubMed  CAS  Google Scholar 

  • Barbas CF III, Amberg W, Simonesits A et al (1993) Selection of human anti-hapten antibodies from semisynthetic libraries. Gene 137: 57–62

    PubMed  CAS  Google Scholar 

  • Bell KD, Ramilo O, Vitetta ES (1993) Combined use of an immunotoxin and cyclosporine to prevent both activated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus. Proc Natl Acad Sci USA 90: 1411–1415

    PubMed  CAS  Google Scholar 

  • Better M, Bernhard SL, Lei SP, Fishwild DM, Lane JA, Carroll SF, Horwitz AH (1993) Potent anti-cd5 ricin-A-chain immunoconjugates from bacterially produced fab’ and f(ab’)2. Proc Natl Acad Sci USA 90: 457–461

    PubMed  CAS  Google Scholar 

  • Bjorn MJ, Ring D, Frankel A (1985) Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins. Cancer Res 45: 1214–1221

    PubMed  CAS  Google Scholar 

  • Blakey DC, Thorpe PE (1988) An overview of therapy with immunotoxins containing ricin or its A-chain. Antibody Immunoconj Radiopharm 1: 1–16

    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 

  • Blakey DC, Skilleter DN, Price RJ, Thorpe PE (1988) Uptake of native and deglycosylated ricin A-chain immunotoxins by mouse liver parenchymal and non-parenchymal cells in vitro and in vivo. Biochim Biophys Acta 968: 172–178

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Burrows FJ, Thorpe PE (1993) Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. Proc Natl Acad Sci USA 90: 8996–9000

    PubMed  CAS  Google Scholar 

  • Byers VS, Baldwin RW (1988) Therapeutic strategies with monoclonal antibodies and immunoconjugates. Immunology 65: 329–335

    PubMed  CAS  Google Scholar 

  • Byers VS, Pimm MV, Pawluczyk I, Lee HM, Scannon PJ, Baldwin RW (1987) Biodistribution of ricin toxin A-chain monoclonal antibody 79IT/36 immunotoxins and the influence of heptic blocking agents. Cancer Res 47: 5277–5283

    PubMed  CAS  Google Scholar 

  • Byers VS, Austin EB, Clegg JA et al (1993) Suppression of antibody responses to ricin A chain ( RTA) by monoclonal anti-RTA antibodies. J Clin Immunol 13: 406–412

    PubMed  CAS  Google Scholar 

  • Campana D, Pui CH (1995) Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance. Blood 85: 1416–1434

    PubMed  CAS  Google Scholar 

  • Campana D, Coustan-Smith E, Behm FG (1991) The definition of remission in acute leukemia with immunologic methods. Bone Marrow Transplant 8: 429–437

    PubMed  CAS  Google Scholar 

  • Casellas P, Jansen FK (1988) Immunotoxin enhancers. In: Frankel AE (ed) Immunotoxins. Kluwer Academic, Norwell, pp 351–371

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Conry RM, Khazaeli MB, Saleh MN, Ghetie V, Vitetta ES, Liu TP, Lobuglio AF (1995) Phase I trial of an anti-CD19 deglycosylated ricin A-chain immunotoxin in non-Hodgkin’s lymphoma: effect of an intensive schedule of administration. J Immunother 18 (4): 231–241

    CAS  Google Scholar 

  • Cumber AJ, Forrester JA, Foxwell BM, Ross WC, Thorpe PE (1985) Preparation of antibody-toxin conjugates. Methods Enzymol 112: 207–225

    PubMed  CAS  Google Scholar 

  • Cuneo A, Wlodarska I, Sayed AM, Piva N, Carli MG, Fagioli F, Tallarico A, Pazzi I, Ferrari L, Cassiman J et al. (1992) Non-radioactive in situ hybridization for the detection and monitoring of trisomy 12 in B-cell chronic lymphocytic leukaemia. Br J Haematol 81: 192–196

    PubMed  CAS  Google Scholar 

  • Denekamp J (1984) Vasculature as a target for tumor therapy. Prog Appl Microcirc 4: 28–38

    Google Scholar 

  • Denekamp J (1990) Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev 9: 267–282

    PubMed  CAS  Google Scholar 

  • Derbyshire EJ, Wawrzynczak EJ (1992) An antimucin immunotoxin bre-3-ricin A-chain is potently and selectively toxic to-human small-cell lung cancer. Int J Cancer 52: 624–630

    PubMed  CAS  Google Scholar 

  • Derbyshire EJ, Stahel RA, Wawrzynczak EJ (1992) Cytotoxic properties of a ricin A-chain immunotoxin recognizing the cluster-5 A antigen associated with human small-cell lung cancer. Cancer Immunol Immunother 35: 417–420

    PubMed  CAS  Google Scholar 

  • Derbyshire EJ, Henry RV, Stahel RA, Wawrzynczak EJ (1996) Potent cytotoxic action of the immunotoxin SWAT l-ricin A-chain against human small lung cancer cell lines. Br J Cancer 66: 444451

    Google Scholar 

  • Drexler HG, Borkhardt A, Janssen JW (1995) Detection of chromosomal translocations in leukemia-lymphoma cells by polymerase chain reaction. Leuk Lymphoma 19: 359–380

    PubMed  CAS  Google Scholar 

  • Engert A, Burrows F, Jung W, Tazzari PL, Stein H, Pfreundschuh M, Diehl V, Thorpe P (1990a) Evaluation of ricin A-chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin’s disease. Cancer Res 50: 84–88

    PubMed  CAS  Google Scholar 

  • Engert A, Martin G, Pfreundschuh M, Amlot P, Hsu SM, Diehl V, Thorpe P (1990b) Anti-tumor effects of ricin A-chain immunotoxins from intact antibodies and Fab’ fragments on solid human Hodgkin’s disease tumors in mice. Cancer Res 50: 2929–2935

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig M, Drillich S, Schön G, Bohlen H, Tesch H, Hansmann M, Barth S, Schindler J, Ghetie V, Uhr J, Vitetta E (1997) A Phase-I study of an antiCD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin’s lymphoma. Blood 1: 403–410

    Google Scholar 

  • Epenetos AA, Snok D, Durbin H, Johnson PM, Taylor-Papadimitriou J (1986) Limitations of radiolabeled monoclonal antibodies for localization of human neoplasms. Cancer Res 46: 3183–3191

    PubMed  CAS  Google Scholar 

  • Faguet GB, Agee JF (1993) Four ricin chain a-based immunotoxins directed against the common chronic lymphocytic leukemia antigen–invitro characterization. Blood 82: 536–543

    PubMed  CAS  Google Scholar 

  • Frankel AE, Ring DB, Tringale F, Hsieh-Ma ST (1985) Tissue distribution of breast cancer-associated antigens defined by monoclonal antibodies. J Biol Resp Modif 4: 273–286

    CAS  Google Scholar 

  • Fulton RJ, Blakey DC, Knowles PP, Uhr JW, Thorpe PE, Vitetta ES (1986) Production of ricin Al, A2, and B chains and characterization of their toxicity. J Biol Chem 261: 5314–5319

    PubMed  CAS  Google Scholar 

  • Fulton RJ, Tucker TF, Vitetta ES, Uhr JW (1988a) Pharmacokinetics of tumor-reactive immunotoxins in tumor-bearing mice: effect of antibody valency and deglycosylation of the ricin A-chain on clearance and tumor localization. Cancer Res 48: 2618–2625

    PubMed  CAS  Google Scholar 

  • Fulton RJ, Uhr JW, Vitetta ES (1988b) 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 

  • Ghetie M, May RD, Till M, Uhr JW, Ghetie V, Knowles PP, Relf M, Brown A, Wallace PM, Janossy G et al (1988) Evaluation of ricin A-chain-containing immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B-cells as potential reagents for in vivo therapy. Cancer Res 48: 2610–2617

    PubMed  CAS  Google Scholar 

  • Ghetie M, Tucker K, Richardson J, Uhr JW, Vitetta ES (1992) The anti-tumor 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 M-A, 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: 702–707

    PubMed  CAS  Google Scholar 

  • Ghetie V, Engert A, Schnell R, Vitetta ES (1995) The in vivo anti-tumor activity of immunotoxins containing two versus one deglycosylated ricin A chains. Cancer Lett 98: 97–101

    PubMed  CAS  Google Scholar 

  • Ghetie MA, Podar EM, Gordon BE, Pantazis P, Uhr JW, Vitetta ES (1996) Combination immunotoxin treatment and chemotherapy in SCID mice with advanced, disseminated Daudi lymphoma. Int J Cancer 68: 93–96

    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

    PubMed  CAS  Google Scholar 

  • Gros O, Gros P, Jansen FK, Vidal H (1985) Biochemical aspects of immunotoxin preparation. J Immunol Methods 81: 283–297

    PubMed  CAS  Google Scholar 

  • Grossbard ML, Gribben JG, Freedman AS et al (1993) Adjuvant immunotoxin therapy with anti-B4blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin’s lymphoma. Blood 81: 2263–2271

    PubMed  CAS  Google Scholar 

  • Gribben JG, Freedman AS, Woo SD et al (1991) All advanced stage non-Hodgkin’s lymphomas with a polymerase chain reaction amplifiable breakpoint of bel-2 have residual cells containing the bel-2 rearrangement at evaluation and after treatment. Blood 78: 3275–3280

    PubMed  CAS  Google Scholar 

  • Hagenbeek A, Martens ACM (1989) Cryopreservation of autologous marrow grafts in acute leukemia: survival of in vivo clonogenic leukemic cells and normal hematopoietic stem cells. Leuk 3: 535–537

    CAS  Google Scholar 

  • Hara H, Luo Y, Haruta Y, Seon BK (1988) Efficient transplantation of human non-T-leukemia cells into nude mice and induction of complete regression of the transplanted distinct tumors by ricin A-chain conjugates of monoclonal antibodies SN5 and SN6. Cancer Res 48: 4673–4680

    PubMed  CAS  Google Scholar 

  • Jansen B, Vallera DA, Jaszcz WB, Nguyen D, Kersey JH (1992) Successful treatment of human acute T-cell leukemia in SCID mice using the anti-CD7-deglycosylated ricin A-chain immunotoxin DA7. Cancer Res 52: 1314–1321

    PubMed  CAS  Google Scholar 

  • Jansen FK, Blythman HE, Carriere D, Casellas P, Diaz J, Gros P, Hennequin JR, Paolucci F, Pau B, Poncelet P et al (1980) High specific cytotoxicity of antibody-toxin hybrid molecules (immunotoxins) for target cells. Immunol Lett 2: 97–102

    CAS  Google Scholar 

  • Jansen FK, Blythman HE, Carriere D, Casellas P, Gros O, Gros P, Laurent JC, Paolucci F, Pau B, Poncelet P et al (1982) Immunotoxins: hybrid molecules combining high specificity and potent cytotoxicity. Immunol Rev 62: 185–216

    PubMed  CAS  Google Scholar 

  • Jin FS, Youle RJ, Johnson VG et al (1991) Suppression of the immune response to immunotoxins with anti-CD4 monoclonal antibodies. J Immunol 146: 1806–1811

    PubMed  CAS  Google Scholar 

  • Katre NV (1993) The conjugation of proteins with polyethylene glycol and other polymers. Adv Drug Delivery Rev 10: 91–114

    CAS  Google Scholar 

  • Kimura Y, Hase S, Kobayashi Y, Kyogoku Y, Ikenaka T, Funatsu G (1988) Structures of sugar chains of ricin D. J Biochem (Tokyo) 103: 944–949

    CAS  Google Scholar 

  • Kitamura K, Takahashi T, Yamaguchi T, Noguchi A, Takashina K, Tsurumi H, Inagake M, Toyokuni T, Hakomori S (1991) Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy. Cancer Res 51: 4310–4315

    PubMed  CAS  Google Scholar 

  • Kitamura K, Takahashi T, Takashina K, Yamaguchi T, Noguchi A, Tsurumi H, Tojokuni T, Hakomori S (1996) Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization. Biochem Biophys Res Commun 171: 1387–1394

    Google Scholar 

  • Knowles PP, Thorpe PE (1987) Purification of immunotoxins containing ricin A-chain and abrin A-chain using Blue Sepharose CL-6B. Anal Biochem 160: 440–443

    PubMed  CAS  Google Scholar 

  • Kuar G, Pai LM, Pastan I (1996) Immunotoxins tageting Le4 damage human endothelial cells in an antibody specific mode: reliance to vascular leak syndrome. 4th international symposium on immunotoxins, p 115

    Google Scholar 

  • Laman JD, Claassen E, Noelle RJ (1996) Functions of CD40 and its ligand, gp39 (CH40L). Crit Rev hnmunol 16: 59–108

    CAS  Google Scholar 

  • Lamb FI, Roberts LM, Lord JM (1985) Nucleotide sequence of cloned cDNA coding for preproricin. Eur J Biochem 148: 265–270

    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 

  • Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14: 233–258

    PubMed  CAS  Google Scholar 

  • Li BY, Ramakrishnan S (1994) Recombinant hybrid toxin with dual enzymatic activities. Potential use in preparing highly effective immunotoxins. J Biol Chem 269 (4): 2652–2658

    PubMed  CAS  Google Scholar 

  • Linsley PS, Wallace PM, Johnson J et al (1992) Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 257: 792–795

    PubMed  CAS  Google Scholar 

  • Masuho Y, Kishida K, Saito M, Umeto N, Hara T (1982) Importance of the antigen-binding valency and the nature of cross-linking bond in ricin A-chain conjugates with antibody. J Biochem 91: 1583–1591

    PubMed  CAS  Google Scholar 

  • May RD, Finkelman F, Uhr JW, Vitetta ES (1990) Evaluation of ricin A-chain-containing immunotoxins directed against different epitopes on the deltA-chain of sIgD on murine B cells. J Immunol 144: 3637–3642

    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

    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

    PubMed  Google Scholar 

  • O’Hare M, Brown AN, Hussain K, Gebhardt A, Watson G, Roberts LM, Vitetta ES, Thorpe PE, Lord JM (1990) Cytotoxicity of a recombinant ricin-A-chain fusion protein containing a proteolytical cleavable spacer sequence. FEBS Lett 273: 200–204

    PubMed  Google Scholar 

  • Okazaki M, Luo Y, Han T, Yoshida M, Seon BK (1993) Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin’s lymphoma and are effectively internalized after binding to the cell surface antigen. Blood 81: 84–94

    PubMed  CAS  Google Scholar 

  • Pai LH, FitzGerald DJ, Tepper M et al (1990) Inhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice. Cancer Res 50: 7750–7753

    PubMed  CAS  Google Scholar 

  • Pantel K, Schlimok G, Braun S, Kutter D, Lindemann F, Schaller G, Funke I, Izbicki JR, Riethmüller G (1993) Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 85: 1419–1424

    PubMed  CAS  Google Scholar 

  • Parham P (1983) On the fragmentation of monoclonal IgGl, IgG2a and IgG2b from BALB/c mice. J Immunol 131: 2895–2902

    PubMed  CAS  Google Scholar 

  • Press OW, Vitetta ES, Farr AG, Hansen JA, Martin PJ (1986) Evaluation of ricin A-chain immunotoxins directed against human T cells. Cell Immunol 102: 10–20

    PubMed  CAS  Google Scholar 

  • Press OW, Martin P, Thorpe PE, Vitetta ES (1988) Ricin A-chain containing immunotoxins directed against different epitopes on the CD2 molecule differ in their ability to kill normal and malignant T cells. J Immunol 141: 4410–4417

    PubMed  CAS  Google Scholar 

  • Ramakrishnan S, Houston LL (1984a) Comparison of the selective cytotoxic effects of immunotoxins containing ricin A-chain or pokeweed antiviral protein and anti-Thy 1.1 monoclonal antibodies. Cancer Res 44: 201–208

    PubMed  CAS  Google Scholar 

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

    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 (1988) Growth factors and other ligands. In: Frankel AE (ed) Immunotoxins. Kluwer Academic, Norwell, pp 297–323

    Google Scholar 

  • Raso V, Griffin T (1980) Specific cytotoxicity of a human immunoglobulin directed Fab’-ricin A conjugate. J Immunol 125: 2610–2616

    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

    PubMed  CAS  Google Scholar 

  • Riechmann L, Clark M, Waldmann H et al (1988) Reshaping human antibodies for therapy. Nature 332: 323–327

    PubMed  CAS  Google Scholar 

  • Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of vascular fluid mediated by the systemic administration of recombinant interleukin-2. J Immunol 137: 1735–1742

    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 et al (1995) Continuous infusion of the anti-CD22 immunotoxin, IgG-RFB4SMPT-dgA in patients with B cell lymphoma: a phase I study. Blood 85: 3457–3465

    PubMed  CAS  Google Scholar 

  • Sharp JG, Joshi SS, Armitage JO et al (1992) Significance of detection of occult non-Hodgkin’s lym- phoma in histologically uninvolved bone marrow by a culture technique. Blood 79: 1074–1080

    PubMed  CAS  Google Scholar 

  • Shen G, Li J, Vitetta ES (1994) Bispecific anti-CD22/anti-CD3-ricin A-chain immunotoxin is cytotoxic to Daudi lymphoma cells but not T cells in vitro and shows both A-chain-mediated and LAK-T mediated killing. J Immunol 152: 2368–2376

    PubMed  CAS  Google Scholar 

  • Shen G, Li J, Ghetie M, Ghetie V, May RD, Till M, Brown AN, Relf M, Knowles P, Uhr JW et al (1988) Evaluation of four CD22 antibodies as ricin A-chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas. Int J Cancer 42: 792–797

    PubMed  CAS  Google Scholar 

  • Siegall CB, Liggitt D, Chace D, Tepper MA, Fell HP (1994) Prevention of immunotoxin-mediated vascular leak syndrome in rats with retention of anti-tumor activity. Proc Natl Acad Sci USA 91 (20): 9514–9518

    PubMed  CAS  Google Scholar 

  • Siegall CB, Haggerty HG, Warner GL, Chace D, Mixan B, Linsley PS and Davidson T (1997) Prevention of immunotoxin-induced immunogenicity by coadministration with CTL4Ig enhances antitumor efficacy. J Immunol 159: 5168–5173

    PubMed  CAS  Google Scholar 

  • Skilleter DN, Paine AJ, Stirpe F (1981) A comparison of the accumulation of ricin by hepatic parenchymal and non-parenchymal cells and its inhibition of protein synthesis. Biochim Biophys Acta 677: 495–500

    PubMed  CAS  Google Scholar 

  • Smyth MJ, Pietersz GA, McKenzie IF (1987) Use of vasoactive agents to increase tumor perfusion and the anti-tumor efficacy of drug-monoclonal antibody conjugates. J Natl Cancer Inst 79: 1367–1373

    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: 227–239

    PubMed  CAS  Google Scholar 

  • Spooner RA, Allen DJ, Epenetos AA, Lord JM (1994) Expression of immunoglobulin heavy chain ricin A-chain fusions in mamalian cells. Mol Immunol 31: 117–125

    PubMed  CAS  Google Scholar 

  • Stanworth DR, Turner MW (1978) Immunochemical analysis of immunoglobulins and their sub-units. In: Weir DM (ed) Handbook of experimental immunology. Blackwell Scientific, Oxford, pp 1–102

    Google Scholar 

  • Stone MJ, Sausville EA, Fay JW, Headlee D, Collins RH, Figg WD, Stetler-Stevenson M, Jain V, Jaffe ES, Solomon D et al (1996) A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD-37-dgRTA, in patients with B-cell lymphoma. Blood 88 (4): 1188–1197

    PubMed  CAS  Google Scholar 

  • Sung C, Dedrick RL, Hall WA, Johnson PA, Youle RJ (1993) The spatial distribution of immunotoxins in solid tumors -assessment by quantitative autoradiography. Cancer Res 53: 2092–2099

    PubMed  CAS  Google Scholar 

  • Svasti J, Milstein C (1972) The disulphide bridges of a mouse immunoglobulin G1 protein. Biochem J 126: 837–850

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Brown AN, Bremner JA Jr, Foxwell BM, Stirpe F (1985a) An immunotoxin composed of monoclonal anti-Thy 1.1 antibody and a ribosome-inactivating protein from Saponaria officinalis: potent anti-tumor effects in vitro and in vivo. J Natl Cancer Inst 75: 151–159

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Detre SI, Foxwell BMJ, Brown ANF, Skilleter DN, Wilson G, Forrester JA, Stirpe F (1985b) Modification of the carbohydrate in ricin with metaperiodate-cyanoborohydride mixtures. Effects on toxicity and in vivo distribution. Eur J Biochem 147: 197–206

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Blakey DC, Brown AN, Knowles PP, Knyba RE, Wallace PM, Watson GJ, Wawrzynczak EJ (1987a) Comparison of two anti-Thy 1.1-abrin A-chain immunotoxins prepared with different cross-linking agents: anti-tumor effects, in vivo fate, and tumor cell mutants. J Natl Cancer Inst 79: 1101–1112

    PubMed  CAS  Google Scholar 

  • Thorpe PE, Wallace PM, Knowles PP, Relf MG, Brown ANF, Watson GJ, Knyba RE, Wawrzynczak EJ, Blakey DC (1987b) 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 ANF, Watson GJ, Blakey DC, Newell DR (1988) Improved anti-tumor effects of immunotoxins prepared with deglycosylated ricin A-chain and hindered disulfide linkages. Cancer Res 48: 6396–6403

    PubMed  CAS  Google Scholar 

  • Till M, May RD, Uhr JW, Thorpe PE, Vitetta ES (1988) An assay that predicts the ability of monoclonal antibodies to form potent ricin A-chain-containing immunotoxins. Cancer Res 48: 1119–1123

    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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Vitetta ES, Fulton RJ, May RD, Till M, Uhr JW (1987) Redesigning nature’s poisons to create antitumor reagents. Science 238: 1098–1104

    PubMed  CAS  Google Scholar 

  • Vitetta ES, Stone M, Amlot P, Fay J, May R, Till M, Newman J, Clark P, Collins R, Cunningham D et al (1991) A phase I immunotoxin trial in patients with B cell lymphoma. Cancer Res 51: 4052–4058

    PubMed  CAS  Google Scholar 

  • Wawrzynczak EJ, Thorpe PE (1987) Methods for preparing immunotoxins: effects of the linkage on activity and stability. In: Vogel CW (ed) Immunoconjugates: antibody conjugates in radioimaging and therapy of cancer. Oxford University Press, New York, pp 28–55

    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: 4062–4067

    PubMed  CAS  Google Scholar 

  • Winkler U, Gottstein C, Schön G, Kapp U, Wolf J, Hansmann M-L, Bohlen H, Thorpe P, Diehl V, Engert A (1994) Successful treatment of disseminated human Hodgkin’s disease in SCID mice with deglycosylated ricin A-chain immunotoxins. Blood 83: 466–475

    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 

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Authors and Affiliations

  1. Department I for Internal Medicine, University of Cologne, 50924, Cologne, Germany

    A. Engert

  2. Developmental Therapeutics Program, National Cancer Institute, Bethesda, MD, 20892, USA

    E. A. Sausville

  3. Cancer Immunobiology Center and Department of Microbiology, The University of Texas, Southwestern Medical Center, Dallas, TX, 75235, USA

    E. Vitetta

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  1. A. Engert
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  2. E. A. Sausville
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  3. E. Vitetta
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Editors and Affiliations

  1. Hollings Cancer Center, Medical University of South Carolina, 171 Ashley Avenue, 29425-2850, Charleston, SC, USA

    Arthur E. Frankel M.D. (Associate Professor of Medicine) (Associate Professor of Medicine)

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© 1998 Springer-Verlag Berlin Heidelberg

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Engert, A., Sausville, E.A., Vitetta, E. (1998). The Emerging Role of Ricin A-Chain Immunotoxins in Leukemia and Lymphoma. In: Frankel, A.E. (eds) Clinical Applications of Immunotoxins. Current Topics in Microbiology and Immunology, vol 234. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-72153-3_2

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  • DOI: https://doi.org/10.1007/978-3-642-72153-3_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-72155-7

  • Online ISBN: 978-3-642-72153-3

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