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Immunotoxins pp 141-159 | Cite as

Immunotoxins containing ricin

  • Daniel A. Vallera
  • Dorothea E. Myers
Part of the Cancer Treatment and Research book series (CTAR, volume 37)

Abstract

Bacterial and plant toxins composed of different protein subunits with diverse biological functions have provided an investigational focal point for researchers in many areas of specialization. Potent catalytic toxins have been linked to monoclonal antibodies (MoAb) for antibody directed cell targeting. These immunotoxins (ITs) have promoted interest for a variety of clinical purposes including cancer therapy, treatment of autoimmune diseases, immunoregulation, and bone marrow transplantation. Although many toxins are currently under investigation by numerous laboratories, the toxin ricin has been used extensively for specific reasons: 1) Ricin is a well defined catalytic inhibitor of protein synthesis at the level of the 60S ribosome. A single molecule of ricin A chain (RTA) in the cytosol can kill a cell, inactivating up to 1500 ribosomes per minute [1]. 2) Ricin has been studied for several centuries, but with accelerated interest over the past 10 years. 3) In the 1970s, unconjugated ricin was clinically tested for its antitumor potential. Although effective, the risk of toxicity to nontarget tissue was prohibitive. 4) Ricin is available in large quantities and because of its binding component is easily purified from seeds of the nonexotic castor bean plant, Ricinus communis.

Keywords

Bone Marrow Transplantation Ammonium Chloride Diphtheria Toxin Autologous Bone Marrow Transplantation Galactose Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Olsnes, S., and Pihl, A. (1976) Abrin, ricin, and their associated immunoglobulins. In: Receptors and recognition, Series B. The Specificity and Action of Animal, Bacterial, and Plant Toxins. P. Cuatrecasas, ed. Chapman and Hall, London, pp 129–173.Google Scholar
  2. 2.
    Endo, Y., Mitsui, K., Motizuki, M., and Tsurugi, K. (1987) The mechanisms of action of ricin and related toxic lectins on eukaryotic ribosomes. J. Biol. Chem., 262, 5908–5912.PubMedGoogle Scholar
  3. 3.
    Nicolson, G.L., and Blaustein, J. (1972). The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces. Biochim. Biophys. Acta, 266, 543–547.PubMedCrossRefGoogle Scholar
  4. 4.
    Olsnes, S., Saltvedt, E., and Pihl, A. (1974) Isolation and comparison of galactose-binding lectins from Abrus precatorius and Ricinus communis. J. Biol. Chem., 249, 803–810.PubMedGoogle Scholar
  5. 5.
    Pardoe, G.I., Bird, G.W., and Uhlenbruck, G. (1969) On the specificity of lectins with a broad agglutination spectrum. I. The nature of the specific receptors of Ricinus communis and Solanum tuberosum lectins. Z Immunitatsforsch, 137, 442–457.Google Scholar
  6. 6.
    Tomita, M., Kurokawa, T., Onozaki, D., Ichiki, N., Osawa, T., and Ukita, T. (1972) Purification of galactose-binding phytoagglutinins and phytotoxin by affinity chromatography using Sepharose. Experientia, 28, 84–85.PubMedCrossRefGoogle Scholar
  7. 7.
    Zentz, C., Frenoy, J.P., and Bourrillon, R. (1978) Binding of galactose and lactose to ricin. Equilibrium studies, Biochim. Biophys. Acta 536, 18–26.PubMedGoogle Scholar
  8. 8.
    Houston, L.L., and Dooley, T.P. (1982) Binding of two molecules of 4-methylumbelliferyl galactose or 4-methylumbelliferyl N-acetylgalactosamine to the B chains of ricin and Ricinus communis agglutinin and to purified ricin B chain. J. Biol. Chem., 257, 4147–4151.PubMedGoogle Scholar
  9. 9.
    Villafranca, J.E., and Robertus, J.D. (1981) Ricin B chain is a product of gene duplication. J. Biol. Chem., 256, 554–556.PubMedGoogle Scholar
  10. 10.
    Rutenber, E., Ready, M., and Robertus, J.D. (1987) Structure and evolution of ricin B chain. Nature, 326, 624–626.PubMedCrossRefGoogle Scholar
  11. 11.
    Youle, R.J., and Neville, D.M., Jr. (1982) Kinetics of protein synthesis inactivation by ricin-anti-Thy 1.1 monoclonal antibody hybrids. J. Biol. Chem. 257, 1598–1601.PubMedGoogle Scholar
  12. 12.
    Lewis, M.S., and Youle, R.J. (1986) Ricin subunit association. Thermodynamics and the role of the disulfide bond on toxicity. J. Biol. Chem., 261, 11571–11577.PubMedGoogle Scholar
  13. 13.
    Mclnstosh, D.P., Edwards, D.C., Cumber, A.J., Parnell, G.D., Dean, C.J., Ross, W.C. and Forrester, J.A. (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.CrossRefGoogle Scholar
  14. 14.
    Thiesen, H.-J., Juhl, H., and 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.PubMedGoogle Scholar
  15. 15.
    Vitetta, E.S., Cushley, W., and Uhr, J.W. (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.PubMedCrossRefGoogle Scholar
  16. 16.
    Vitetta, E.S., Fulton, R.J., and Uhr, J.U. (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.PubMedCrossRefGoogle Scholar
  17. 17.
    Salisbury, J.L., Condeelis, J.S., and Satir, P. (1980) Role of coated vesicles, microfilaments, and calmodulin in receptor-mediated endocytosis by cultured B lymphoblastoid cells. J. Cell. Biol, 87, 132–141.PubMedCrossRefGoogle Scholar
  18. 18.
    Nicolson, G., Lacorbiere, M., and Hunter, T. (1975) Mechanism of cell entry and toxicity of an affinity-purified lectin from Ricinus communis and its differential effect on normal and virus-transformed fibroblasts. Cancer Res., 35, 144–155.PubMedGoogle Scholar
  19. 19.
    Youle, R.J., Murray, G.J., and Neville, D.M., Jr. (1981) Studies on the galactose-binding site of ricin and the hybrid toxin Man-6P-ricin. Cell, 23, 551–559.PubMedCrossRefGoogle Scholar
  20. 20.
    Olsnes, S., and Pihl, A. (1982) Toxic lectins and related proteins. In: Molecular Action of Toxins and Viruses. P. Cohen, ed. Elsevier, Amsterdam, pp 51–105.Google Scholar
  21. 21.
    Olsnes, S. (1977) Abrin and ricin: Two toxic lectins inactivating eukaryotic ribosomes. In: Perspectives in Toxicology. A.W. Bernheimer, ed. John Wiley & Sons, New York, pp 121–147.Google Scholar
  22. 22.
    Simmons, B.M., Stahl, P.D., and Russell, J.H. (1986) Mannose receptor-mediated uptake of ricin toxin and ricin A chain by macrophages. J. Biol. Chem., 261, 7912–7920.PubMedGoogle Scholar
  23. 23.
    Fox, C.F., and Das, M. (1979) Internalization and processing of the EGF receptor in the induction of DNA synthesis in cultured fibroblasts: The endocytic activation hypothesis. J. Supramol. Struct., 10, 199–214.PubMedCrossRefGoogle Scholar
  24. 24.
    Goldstein, J.C., Anderson, R.G., and Brown, M.S. (1979) Coated pits, coated vesicles, and receptor mediated endocytosis. Nature (Lond.), 279, 679–685.CrossRefGoogle Scholar
  25. 25.
    Gordon, P., Carpentier, J.L., Cohen, S., and Orci, L. (1978) Epidermal growth factor: Morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. Proc. Natl. Acad. Sci. USA, 75, 5025–5029.CrossRefGoogle Scholar
  26. 26.
    Manske, J.M., Buchsbaum, D.J., Azemove, S.M., Hanna, D.E., and Vallera, D.A. (1986) Antigenic modulation by anti-CD5 immunotoxins. J. Immunol., 136, 4721–4728.PubMedGoogle Scholar
  27. 27.
    Youle, R.J., Murray, G.J., and Neville, D.M., Jr. (1979) Ricin linked to monophosphopentamannose binds to fibroblast lysosomal hydrolase receptors, resulting in a cell-type specific toxin. Proc. Natl. Acad. Sci. USA, 76, 5559–5562.PubMedCrossRefGoogle Scholar
  28. 28.
    Youle, R.J., and Neville, D.M., Jr. (1980) Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin. Proc. Natl. Acad. Sci. USA, 77, 5483–5486.PubMedCrossRefGoogle Scholar
  29. 29.
    Houston, L.L., and Nowinski, R.C. (1981) Cell-specific cytotoxicity expressed by a conjugate of ricin and murine monoclonal antibody directed against Thy 1.1 antigen. Cancer Res., 41, 3913–3917.PubMedGoogle Scholar
  30. 30.
    Thorpe, P.E., Mason, D.W., Brown, A.N., Simmonds, S.J., Ross, W.C., Cumber, A.J., and Forrester, J.A. (1982) Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate. Nature, 297, 594–596.PubMedCrossRefGoogle Scholar
  31. 31.
    Neville, D.M., Jr., and Youle, R.J. (1982) Monoclonal antibody-ricin or ricin A chain hybrids: Kinetic analysis of cell killing for tumor therapy. Immunol. Rev., 62, 75–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Vallera, D.A., Youle, R.J., Neville, D.M., Jr., and Kersey, J.H. (1982) Bone marrow transplantation across major histocompatibility barriers. V. Protection of mice from lethal graft-versus-host disease by pretreatment of donor cells with monoclonal anti-Thy-1.2 coupled to the toxin ricin. J. Exp. Med., 155, 949–954.PubMedCrossRefGoogle Scholar
  33. 33.
    Vallera, D.A., Soderling, C.C., and Grosz, C.G. (1985) Assessment of immunocompetence by limiting dilution analysis in long-term T cell depletion chimeras transplanted across the MHC barrier. Transplantation, 40, 311–316.PubMedCrossRefGoogle Scholar
  34. 34.
    Vallera, D.A., Ash, R.C., Zanjani, E.D., Kersey, J.H., LeBien, T.L., Beverley, P.C., Neville, D.M., Jr., and Youle, R.J. (1983) Anti-T cell reagents for human bone marrow transplantation: Ricin linked to three monoclonal antibodies. Science, 22, 8512–8515.Google Scholar
  35. 35.
    Esworthy, R.S., and Neville, D.M., Jr. (1984) A comparative study of ricin and diphtheria toxin-antibody-conjugate kinetics on protein synthesis inactivation. J. Biol. Chem., 250, 11496–11504.Google Scholar
  36. 36.
    Oladapo, J.M., Goodall, A.H., de Koning, R., Parmar, J., Brown, D., and Thomas, H.C. (1984) In vitro and in vivo cytotoxic activity of native and ricin conjugated monoclonal antibodies to HBs antigen for Alexander primary liver cell carcinoma cells and tumours. Gut, 25, 619–623.PubMedCrossRefGoogle Scholar
  37. 37.
    Quinones, R.R., Youle, R.J., Kersey, J.H., Zanjani, E.D., Azemove, S.M., Soderling, C.C., LeBien, T.W., Beverley, P.C., Neville, D.M., Jr., and Vallera, D.A. (1984) Anti-T cell monoclonal antibodies conjugated to ricin as potential reagents for human GVHD prophylaxis: Effect on the generation of cytotoxic T cells in both peripheral blood and bone marrow. J. Immunol., 132, 678–683.PubMedGoogle Scholar
  38. 38.
    Stong, R.C., Youle, R.J., and Vallera, D.A. (1984) Elimination of clonogenic T-leukemic cells from human bone marrow using Anti-Mr 65,000 protein immunotoxins. Cancer Res., 44, 3000–3006.PubMedGoogle Scholar
  39. 39.
    Vallera, D.A., Quinones, R.R., Azemove, S.M., and Soderling, C.C. (1984) Monoclonal antibody-toxin conjugates reactive against human T lymphocytes: A comparison of antibody linked to intact ricin toxin with antibody linked to ricin A chain. Transplantation, 37, 387–392.PubMedCrossRefGoogle Scholar
  40. 40.
    Weil-Hillman, G., Runge, W., Jansen, F.K., and Vallera, D.A. (1985) Cytotoxic effect of Anti-M. 67,000 protein immunotoxins on human tumors in a nude mouse model. Cancer Res., 45, 1328–1336.PubMedGoogle Scholar
  41. 41.
    Paraskeva, C., Buckle, B.G., and Thorpe, P.E. (1985) Selective killing of contaminating human fibroblasts in epithelial cultures derived from colorectal tumors using an anti Thy-1 antibody-ricin conjugate. Br. J. Can., 51, 131–134.CrossRefGoogle Scholar
  42. 42.
    Nakahara, K., Kaplan, D., Bjorn, M., and Fathman, C.G. (1985) The effectiveness of anti-Ia-immunotoxins in the suppression of MLR. Transplantation, 40, 62–67.PubMedCrossRefGoogle Scholar
  43. 43.
    Colombatti, M., and Bron, C. (1985) Sensitivity of target cells of immunotoxins: Possible role of cell-surface antigens. Immunol. 55, 331–338.Google Scholar
  44. 44.
    Leonard, J.E., Wang, Q.C., Kaplan, N.O., and Royston, I. (1985) Kinetics of protein synthesis inactivation in human T-lymphocytes by selective monoclonal antibody-ricin conjugates. Cancer Res., 45, 5263–5269.PubMedGoogle Scholar
  45. 45.
    Gregg, E.O., Bridges, S.H., Youle, R.J., Longo, D.L., Houston, L.L., Glennie, M.J., Stevenson, F.K., and Green, I. (1987) Whole ricin and recombinant ricin A chain idiotypespecific immunotoxins for therapy of the guinea pig L2C B cell leukemia. J. Immunol., 138, 4502–4508.PubMedGoogle Scholar
  46. 46.
    Weil-Hillman, G., Uckun, F.M., and Vallera, D.A. (1987) Combined immunochemotherapy of human solid tumors in nude mice. Cancer Res., 47, 579–585.PubMedGoogle Scholar
  47. 47.
    Uckun, F.M., Vallera, D.A., and Wee, S.-L. (1985) B lymphocyte regulation of human hematopoiesis. J. Immunol., 135, 3817–3822.PubMedGoogle Scholar
  48. 48.
    Stong, R.C., Uckun, F.M., Youle, R.J., Kersey, J.H., and Vallera, D.A. (1985) Use of multiple T-cell directed intact ricin immunotoxins for autologous bone marrow transplantation. Blood, 66, 627–635.PubMedGoogle Scholar
  49. 49.
    Uckun, F.M., Azemove, S.M., Myers, D.E., and Vallera, D.A. (1985) Anti-CD2 (T, p50) intact ricin immunotoxins for GVHD-prophylaxis in allogeneic bone marrow transplantation. Leukemia Research, 10, 145–153.CrossRefGoogle Scholar
  50. 50.
    Godai, A., Fodstad, O., Morgan, A.C., and Pihl, A. (1986) Human melanoma cell lines showing striking inherent differences in sensitivity to immunotoxins containing holotoxins. J. Natl. Cancer Inst., 77, 1247–1253.Google Scholar
  51. 51.
    Manske, J.M., Buchsbaum, D.J., Hanna, D.E., and Vallera, D.A. (1987) Anti-CD5 radioimmunotoxins: Cytotoxic effects on human tumors in vitro and in a nude mouse model. J. Natl. Cancer Inst., submitted.Google Scholar
  52. 52.
    Youle, R.J., Uckun, F.M., Vallera, D.A., and Colombatti, M. (1986) Immunotoxins show rapid entry of diphtheria toxin but not ricin via the T3 antigen. J. Immunol., 136, 93–98.PubMedGoogle Scholar
  53. 53.
    Marsh, J.W., and Neville, D.M., Jr. (1986) Kinetic comparison of ricin immunotoxins: Biricin conjugate has potentiated cytotoxicity. Biochemistry, 25, 4461–4467.PubMedCrossRefGoogle Scholar
  54. 54.
    Youle, R.J., and Colombatti, M. (1985) Immunotoxins: Monoclonal antibodies linked to toxic proteins for bone marrow transplantation and cancer therapy. In: Monoclonal Antibodies in Cancer: Advances in Diagnosis and Treatment. J.A. Roth, ed. Futura Pub. Co., Mt. Kisco, N.Y., pp 173–213.Google Scholar
  55. 55.
    Thorpe, P.E., Ross, W.C., Brown, A.N., Myers, C.D., Cumber, A.J., Foxwell, B.J., and Forrester, J.T. (1986) 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.CrossRefGoogle Scholar
  56. 56.
    Foxwell, B.M., Ross, W.C., and Thorpe, P.E. (1984) Antibody-ricin conjugates: A method of linkage which blocks the galactose binding site of ricin. Behring Inst. Mitt., 74, 101–107.PubMedGoogle Scholar
  57. 57.
    Vitetta, E.S. (1986) Synergy between immunotoxins prepared with native ricin A chains and chemically-modified ricin B chains. J. Immunol., 136, 1880–1887.PubMedGoogle Scholar
  58. 58.
    Lamb, F.I., Roberts, L.M., and Lord, J.M. (1985) Nucleotide sequence of cloned cDNA coding for preproricin. Eur. J. Biochem., 148, 265–270.PubMedCrossRefGoogle Scholar
  59. 59.
    Colombatti, M., Greenfield, L., and Youle, R.J. (1986) Cloned fragment of diphtheria toxin linked to T cell-specific antibody identified regions of B chain active in cell entry. J. Biol. Chem., 261, 3030–3035.PubMedGoogle Scholar
  60. 60.
    Nicolson, G.L., Blaustein, J., and Etzler, M.E. (1974) Characterization of two plant lectins from Ricinus communs and their quantitative interaction with a murine lymphoma. Biochemistry, 13, 196–204.PubMedCrossRefGoogle Scholar
  61. 61.
    Myers, D.E., Uckun, F.M., Swaim, S.E., and Vallera, D.A. (1987) Heterobifunctional crosslinking reagents useful in the preparation of intact ricin-monoclonal antibody immunotoxins. Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March, p 80.Google Scholar
  62. 62.
    Jansen, F.K., Blythman, H.E., Carriere, D., Cassellas, P., Gros, O., Laurent, J.C., Paolucci, F., Pau, B., Poncelet, P., Richer, G., Vidal, H., and Voisin, G.A. (1982) Immunotoxins: Hybrid molecules combining high specificity and potent cytotoxicity. Immunol. Rev., 62, 185–216.PubMedCrossRefGoogle Scholar
  63. 63.
    Killen, J.A., and Lindstrom, J.M. (1984) Specific killing of lymphocytes that cause experimental autoimmune myasthenia gravis by ricin toxin-acetylcholine receptor conjugates. J. Immunol., 133, 2549–2553.PubMedGoogle Scholar
  64. 64.
    Oeltmann, T.N., and Heath, E.C. (1979) A hybrid protein containing the toxic subunit of ricin and the cell-specific subunit of human chorionic gonadotropin. II. Biological properties. J. Biol. Chem., 254, 1028–1032.PubMedGoogle Scholar
  65. 65.
    Uckun, F.M., Stong, R.C., Youle, R.J., and Vallera, D.A. (1985) Combined ex vivo treatment with immunotoxins and mafosfamid: A novel immunochemotherapeutic approach for elimination of neoplastic T cells from autologous marrow grafts. J. Immunol., 134, 3504–3515.PubMedGoogle Scholar
  66. 66.
    Uckun, F.M., Gajl-Peczalska, K., Myers, D.E., Kersey, J.H., Colvin M., and Vallera, D.A. (1987) Marrow purging in autologous bone marrow transplantation for T-lineage acute lymphoblastic leukemia: Efficacy of ex vivo treatment with immunotoxins and 4-hydroperoxycyclophosphamide against fresh leukemia marrow progenitor cells. Blood, 69, 361–366.PubMedGoogle Scholar
  67. 67.
    Uckun, F.M., Gajl-Peczalska, K.J., Kersey, J.H., Houston, L.L., and Vallera, D.A. (1986) Use of a novel colony assay to evaluate the cytotoxicity of an immunotoxin containing pokeweed antiviral protein against blast progenitor cells freshly obtained from patients with common B-lineage acute lymphoblastic leukemia. J. Exp. Med., 163, 347–368.PubMedCrossRefGoogle Scholar
  68. 68.
    Zvickian, J., Johnson, V., and Youle, R. (1987) Immunotoxin therapy of central nervous system neoplasia. Abstract of the annual meeting of the Association of Neurological Surgeons, Dallas, Texas.Google Scholar
  69. 69.
    Sandvig, K., Olsnes, S., and Pihl, A. (1976) Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J. Biol. Chem., 251, 3977–3984.PubMedGoogle Scholar
  70. 70.
    Neufeld, E.F., and Ashwell, G. (1980) Carbohydrate recognition systems for receptor-mediated pinocytosis. In: The Biochemistry of Glycoproteins and proteoglycans. W.J. Lennarz, ed. Plenum, New York, pp 241–266.Google Scholar
  71. 71.
    Blakey, D.C., Watson, G.J., Knowles, P.P., and Thorpe, P.E. (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, 947–9952.PubMedGoogle Scholar
  72. 72.
    Volkman, D.J., Ahmad, A., Fauci, A.S., and Neville, D.M., Jr. (1982) Selective abrogation of antigen-specific human B cell responses by antigen-ricin conjugates. J. Exp. Med., 156, 634–639.PubMedCrossRefGoogle Scholar
  73. 73.
    Olsberg, C.A., Mikiten, T.M., and Krolick, K.A. (1985) Selective in vitro inhibition of an antibody response to purified acetylcholine receptor by using antigen-ricin A chain immunotoxin. J. Immunol., 135, 3062–3067.PubMedGoogle Scholar
  74. 73.
    Olsberg, C.A., Mikiten, T.M., and Krolick, K.A. (1985) Selective in vitro inhibition of an antibody response to purified acetylcholine receptor by using antigen-ricin A chain immunotoxin. J. Immunol., 135, 3062–3067.PubMedGoogle Scholar
  75. 75.
    DeDuve, C., deBarsy, T., Poole, B., Trouet, A., Tulkens, P., and Van Hoof, F. (1974) Lysosomotropic agents. Biochem. Pharmacol., 23, 2495–2531.CrossRefGoogle Scholar
  76. 76.
    Buchsbaum, D.J., Nelson L.A., Hanna, D.E., and Vallera, D.E. (1987) Human leukemia cell binding and killing by anti-CD5 radioimmunotoxins. Int. J. Rad. Oncol. Biol. Phys., 13, 1701–1712.CrossRefGoogle Scholar
  77. 77.
    Laurent, G., Pris, J., Farcet, J.-P., Carayon, P., Blythman, H., Casellas, P., Poncelet, P., and Jansen, F.K. (1986) Effects of therapy with T101 ricin A-chain immunotoxin in two leukemia patients. Blood, 67, 1680–1687.PubMedGoogle Scholar
  78. 78.
    Frankel, A.E., Schlossman, D.M., Borowitz, M.J., and Hertler, A.A. (1986) A phase I study of T101 RTA immunotoxin in refractory chronic lymphocytic leukemia. Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, p. 19.Google Scholar
  79. 79.
    Spitler, L.E., del Rio, M., Khentigan, A., Wedel, N.I., Brophy, N.A., Miller, L.L., Harkonen, W.S., Rosendorf, L.L., Lee, H.M., Mischak, R.P., Kawahata, R.T., Stoudemire, J.B., Fradkin, L.B., Bautista, E.E., and Scannon, P.J. (1987) Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res., 47, 1717–1723.PubMedGoogle Scholar

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© Kluwer Academic Publishers 1988

Authors and Affiliations

  • Daniel A. Vallera
  • Dorothea E. Myers

There are no affiliations available

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