Abstract
Immunotoxins consist of monoclonal or polyclonal antibodies conjugated to bacterial or plant toxins. The toxins used are typically of the A-B type in which a toxic A chain is coupled to a B chain responsible for cell binding and facilitation of A chain entry into the cytosol. Two broad strategies have been followed: coupling intact toxins, or A chains alone, to antibodies. This review examines current progress inin vitro andin vivo research, including recent clinical studies, concentrating principally on ricin or ricin A chain conjugates. The future role of conjugates using membrane-acting toxins, immunolysins, is also discussed.
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Baker, M. C., Lawler, S. D., Harris, H., Barrett, A. and Powles, R. L. (1986) Radiation damage in patients treated by total body irradiation, bone marrow grafting and cyclosporin.Radiation Res. 105:413–424.
Bashford, C. L., Alder, G. M., Patel, K. and Pasternak, C. A. (1984) Common action of certain viruses, toxins and activated complement: pore formation and its prevention by extracellular calcium.Biosci. Rep. 4:797–805.
Bernier, L. G., Page, M., Gaudreault, R. C. and Joly, L. P. (1984) A chlorambucil-anti-CEA conjugate cytotoxic for human colon adenocarcinoma cells in vitro.Br. J. Cancer 49:245–246.
Bjorn, M. J., Ring, D. and Frankel, A. (1985) Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins.Cancer Res. 45:1214–1221.
Blakey, D. C. and Thorpe, P. E. (1988) An overview of therapy with immunotoxins containing ricin or its A-chain.Antibody, Immunoconjugates and Radiopharmaceuticals 1:1–16.
Blakey, D. C., Watson, G. J., Knowles, P. P. and Thorpe, P. E. (1987) Effect of chemical deglycosylation of ricin A-chain on thein vivo fate and cytotoxic activity of an immunotoxin composed of ricin A-chain and Anti-Thy 1.1 antibody.Cancer Res. 47:947–952.
Butterworth, A. G. and Lord, J. M. (1983) Ricin andRicinus communis agglutinin subunits are all derived from a single-size polypeptide precursor.Eur. J. Biochem 137:57–65.
Byers, V., Henslee, P., Kernan, N., Blazar, B., Gingrich, R., Phillips, G., Antin, J., Mischak, R., O'Reilly, R. and Scannon, P. (1988) Therapeutic response to a pan-T lymphocyte monoclonal antibody ricin A chain immunotoxin in steroid refractory graft versus host disease (GVHD). In:Proceedings of International Symposium on Immunotoxins, Durham, N.C., USA.
Byers, V. S., Pimm, M. V., Scannon, P. J., Pawluczyk, I. and Baldwin, R. W. (1987) Inhibition of growth of human tumor xenografts in athymic mice treated with ricin toxin A chain monoclonal antibody 791 T/36 conjugates.Cancer Res. 47:5042–5046.
Campbell, A. K. and Morgan, B. P. (1985) Monoclonal antibodies demonstrate protection of polymorphonuclear leukocytes against complement attack.Nature 317:164–166.
Carrasco, L., Fernandez-Puentes, C. and Vasquez, D. (1975) Effects of ricin on the ribosomal sites involved in the interaction of the elongation factors.Eur. J. Biochem. 54:499–503.
Casselas, P., Bourrie, B. J. P., Gros, P. and Jansen, F. K. (1984) Kinetics of cytotoxicity induced by immunotoxins: enhancement by lysosomotropic amines and carboxylic ionophores.J. Biol. Chem. 259:9359–9364.
Casselas, P., Brown, J. P., Gros, O., Gros, P., Hellstrom, I., Jansen, F. K., Poncelet, P., Roncucci, R., Vidal, H. and Hellstrom, K. E. (1982) Human melanoma cells can be killedin vitro by an immunotoxin specific for melanoma-associated antigen p97.Int. J. Cancer 30:437–443.
Collier, R. J. (1977) Inhibition of protein synthesis by exotoxins fromCorynebacterium diphtheriae andPseudomonas aeruginosa. In:The Specificity and Action of Animal, Bacterial and Plant Toxins (Receptors and Recognition Series B, Vol. 1), Cuatrecasas, P. (ed), Chapman and Hall, London, pp. 69–101.
Draper, R. K. and Simon, M. I. (1980) Entry of diphtheria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement.J. Cell Biology 87:849–854.
Drobniewski, F. A. and Ellar, D. J. (1988) Investigation of the membrane lesion inducedin vitro by two mosquitocidal δ-endotoxins ofBacillus thuringiensis.Current Microbiol. 16:195–199.
Drobniewski, F. A., Knowles, B. H. and Ellar, D. J. (1987) Nonspecific ionic effects on the cytolytic and haemolytic properties ofBacillus thuringiensis δ-endotoxins.Current Microbiol. 15:295–299.
Drobniewski, F. A., Sawyer T. J. and Ellar D. J. (1986) The mode of action of the mosquitocidal δ-endotoxin ofBacillus thuringinensis var.darmstadiensis. In:Bacterial Protein Toxins (Zbl. Bakkt. vol.15), eds. Falmagne, P., Alouf, J. E., Fehrenbach, F. J., Jeljaszewicz, J. and Thelestam M., Gustav Fischer, Stuttgart, pp. 55–56.
Drobniewski, F. A., Thorpe P. E., Wallace P. M. and Wawrzynczak E. (1988). The potential of membrane-acting Toxins for Targeted Cancer Therapy (ed. Gregoriadis G.). In:Targeting of Drugs: Anatomical and Physiological Considerations, NATO ASI Series, Plenum Press, pp. 103–108.
Eiklid, K., Olsnes, S. and Pihl, A. (1980) Entry of lethal doses of abrin, ricin, and modeccin into the cytosol of HeLa cells.Exp. Cell. Res. 126:321–326.
Ellar, D. J., Knowles, B. H., Haider, M. Z. and Drobniewski, F. A. (1986) Investigation of the specificity, cytotoxic mechanisms and relatedness ofBacillus thuringiensis delta-endotoxins from different pathotypes. In:Bacterial Protein Toxins (Zbl. Bakkt. vol. 15) eds. Falmagne, P., Alouf, J. E., Fehrenbach, F. J., Jeljaszewicz, J. and Thelestam, M., Gustav Fischer, Stuttgart, pp. 41–48.
Ellar, D. J., Thomas, W. E., Knowles, B. H., Ward, E. S., Todd, J., Drobniewski, F., Lewis, J., Sawyer, T., Last, D. and Nicholls, C. (1985) Biochemistry, genetics and mode of action ofBacillus thuringiensis delta-endotoxins. In:Molecular Biology of Microbial Differentiation, eds. Hoch, J. and Setlow, P., Am. Soc. Microbiol., Washington, D.C., pp. 230–240.
Embleton, M. J., Rowland, G. F., Simmonds, R. G., Jacobs, E., Marsden, C. H. and Baldwin, R. W. (1983) Selective cytotoxicity against human tumour cells by a vindescine-monoclonal antibody conjugate.Br. J. Cancer 47:43–49.
Endo, Y., Mitsui, K., Motizuki, M. and Tsurugi, K. (1987) Mechanism of action of ricin and related toxic lectins.J. Biol. Chem. 262:5908–5912.
Føstad, O., Kvalheim, G., Godal, A., Lotsberg, J., Aamdal, S., Host, H. and Pihl, A. (1984) Phase 1 study of the plant protein ricin.Cancer Res. 44:862–865.
Filipovich, A. H., Vallera, D. A., Youle, R. J., Haake, R., Blazar, B. R., Arthur, D., Neville, D. M., Ramsay, N. K., McGlave, P. and Kersey, J. H. (1987) Graft-versus-host-disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. A pilot study using immunotoxins for T cell depletion of donor bone marrow.Transplantation 44:62–69.
Filipovich, A. H., Vallera, D. A., Youle, R. J., Quinones, R. R., Neville, D. M. and Kersey, J. H. (1985) Ex-vivo treatment of donor bone-marrow with anti-T cell immunotoxins for prevention of graft-versus host disease.Lancet i:469–472.
FitzGerald, D. J., Bjorn, M. J., Ferris, R. J., Winkelhake, J. L., Frankel, A. E., Hamilton, T. C., Ozols, R. F., Willingham, M. C. and Pastan, I. (1987) Antitumor activity of an immunotoxin in a nude mouse model of human ovarian cancer.Cancer Res. 47:1407–1410.
Flickinger, R. A. and Trost, S. R. (1976) Cytotoxicity of antibody-phospholipase C conjugates on cultured Friend leukaemia cells.Eur. J. Cancer 12:159–160.
Foxwell, B. M. J., Donovan, T. A., Thorpe, P. E. and Wilson, G. (1985) The removal of carbohydrates from ricin with endoglycosidases H, F and D and α-mannosidase.Biochim. Biophys. Acta. 840:193–203.
Fulton, R. J., Uhr, J. W. and Vitetta, E. S. (1988)In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain.Cancer Res. 48:2626–2631.
Ghetie, M.-A., May, R. D., Till, M., Uhr, J. W., Ghetie, V., Knowles, P., Relf, M., Brown, A., Wallace, P. M., Janossy, G., Amlot, P., Vitetta, E. S. and Thorpe, P. E. (1988) Evaluation of ricin A chain-containing immunotoxins directed against CD 19 and CD 22 antigens on normal and malignant human B-cells as potential reagentsin vivo therapy.Cancer Res. 48: 2610–2617.
Ghose, T. and Guclu, A. (1974) Cure of a mouse lymphoma with radioidinated antibody.Eur. J. Cancer 10:787–792.
Gorin, N. C., Douay, L., Laporte, J. P., Lopez, M., Zittoun, R., Rio, B., David, R., Stachowiak, J., Jansen, J., Cazellas, P., Poncelet, P., Liance, M. C., Voisin, G. A., Salmon, C., LeBlanc, G., Deloux, J., Najman, A. and Duhamel, G. (1985) Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T101 in the treatment of leukemia and lymphoma: First clinical observations.Cancer Treat. Rep. 69:953–959.
Hale, G. (1988) Bone marrow therapy with monclonal antibodies.Biochem. Pharmacol. 37:3207–3214.
Hara, H. and Seon, B. K. (1987) Complete suppression ofin vivo growth of human leukemia cells by specific immunotoxins: nude mouse models.Proc. Natl. Acad. Sci. 84:3390–3394.
Hayward, A. R., Murphy, S., Githens, J. et al. (1982) Failure of a pan-reactive anti-T cell antibody, OKT 3, to prevent graft-versus-host disease in severe combined immunodeficiency.J. Pediatrics 100:665–668.
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.
Jansen, F. K., Blythman, H. E., Carriere, D., Casellas, P., Gros, O., Gros, P., Laurent, J. C., Paolocci, F., Pau, B., Poncelet, P., Richer, G., Vidal, H. and Voison, G. A. (1982) Immunotoxins: hybrid molecules combining high specificity and potent cytotoxicity.Immunol. Reviews 62:185–216.
Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S. and Winter, G. (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse.Nature 321:522–525.
Jonker, M. and Den Brok, J. H. A. (1987) Idiotype switching of CD4-specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti-mouse IgG antibodies.Eur. J. Immunol. 17:1547–1553.
Kemshead, J. T., Heath, L., Gibson, F. M., Katz, F., Richmond, F., Treleavan, J. and Ugelstad, J. (1986) Magnetic microspheres and monoclonal antibodies for the depletion of neuroblastoma cells from bone marrow: Experiences, improvements and observations.Br. J. Cancer 54:771–778.
Kernan, N. A., Byers, V., Scannon, P. J., Mischak, R. P., Brochstein, J., Flomenberg, N., Dupont, B. and O'Reilly, R. J. (1988) Treatment of steroid-resistant acute graft-versus-host disease byin vivo administration of an anti-T cell ricin A chain immunotoxin.JAMA 259:3154–3157.
Kishida, K., Mauho, Y., Saito, M., Hara, T. and Fuji, H. (1983) Ricin A-chain conjugated with monoclonal anti-L1210 antibody.In vitro andin vivo antitumor activity.Cancer Immunol. Immunother. 16:93–97.
Knowles, B. H. and Ellar, D. J. (1986) Characterisation and partial purification of a plasma membrane receptor forBacillus thuringiensis var.kurstaki lepidopteran-specific delta-endotoxin.J. Cell Sci. 83:89–101.
Knowles, P. P. and Thorpe, P. E. (1987) Purification of immunotoxins containing ricin A chain and abrin A chain using blue Sepharose CL-6B.Anal. Biochem. 160:440–443.
Kondo, T., Fitzgerald, D., Chaudhary, V. K., Adhya, S. and Pastan, I. (1988) Activity of immunotoxins constructed with modifiedPseudomonas exotoxin A lacking the cell recognition domain.J. Biol. Chem. 263:9470–9475.
Krolick, K. A., Uhr, J. W., Slavin, S. and Vitetta, E. S. (1982)In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins.J. Exp. Med. 155:1797–1809.
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.
Latif, Z. A., Lozzio, B. B., Wust, C. J., Krauss, S., Aggio, M. C. and Lozzio, C. B. (1980) Evaluation of drug-antibody conjugates in the treatment of human myelosarcomas transplanted in nude mice.Cancer 45:1326–1333.
Linder, R. (1984) Alteration of mammalian membranes by the co-operative and antagonistic actions of bacterial proteins.Biochim. Biophys. Acta 779:423–435.
Lord, J. M. and Roberts, L. M. (1987) Plant toxins.Microbiological Sciences 4:376–378.
Masuho, Y., Kishida, K., Saito, M., Umemoto, N. and Hara, T. (1982). Importance of the antigen-binding valency and the nature of the cross-linking bond in ricin A-chain conjugates with antibody.J. Biochem. 91:1583–1591.
Mathe, G., Loc., T. B. and Bernard, J. (1958) Effet sur la leucemie 1210 de la souris d'un combinasion par diazotation d'A methopterine et de γ-globulines de hamsters porteurs de cette leucemie par heterogreffe.C.R. Acad. Sci. 246:1626–1628.
Mew, D., Wat, C., Towers, G. H. N. and Levy, J. G. (1983) Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-haematoporphyrin conjugates.J. Immunol. 130:1473–1477.
McIntosh, D. P., Edwards, D. C., Cumber, A. J., Parnell, G. D., Dean, C. J., Ross, W. C. J. 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 Letts. 164:17–20.
Moa, G., Nicolae, M., Laky, M., Bancu, A. and Moraru, I. (1988) In vivo follow up of the cytotoxic effect of ricin toxin vectorized by multivalent hybrid antibody on target cells.Immunol. Letters 17:177–182.
Moolten, F., Zajdel, S. and Cooperband, S. (1976) Immunotherapy of experimental animal tumours with antitumour antibodies conjugated to diphtheria toxin or ricin.Ann. N.Y. Acad. Sci. 277:690–699.
Montford, W., Villafranca, J. E., Monzingo, A. F., Ernst, S. R., Katzin, B., Rutenbert, E., Xuong, N. H., Hamlin, R. and Robetus, J. D. (1987) The three dimensional structure of ricin at the 2.8 Å.J. Biol. Chem. 262:5398–5403.
Neuberger, M. S. (1985). Making novel antibodies by expressing transfected immunoglobulin genes.Trends in Biochem. Sci. 10:347–9.
Nolan, R. D., Grasmuk, H. and Drews, J. (1976) The binding of tritiated elongation factors 1 and 2 to ribosomes from Krebs II mouse ascites tumor cells.Eur. J. Biochem. 64:69–75.
O'Hare, M., Roberts, L. M., Thorpe, P. E., Watson, G. J., Prior, B. and Lord, J. M. (1987) Expression of ricin A chain inEscherichia coli.FEBS Letts 216:73–78.
Olsnes, S. (1977) Abrin and Ricin: two toxic lectins inactivating eukaryotic ribosomes. In:Perspectives in Toxicology, (Bernheimer, A. W., ed), John Wiley and Sons, New York., pp. 122–146.
Olsnes, S. and Pihl, A. (1977) Abrin, ricin and their associated agglutinins. In:The Specificity and Action of Animal, Bacterial and Plant Toxins (Receptors and Recognition Series B. Vol. 1), Cuatrecasas, P., (ed.), Chapman and Hall, London, pp. 131–173.
Olsnes, S. and Pihl, A. (1982) Toxic lectins and related proteins. In:Molecular Action of Toxins and Viruses, (Cohen, P. and van Heyningen, S., eds.), Elsevier Biomedical Press, New York, pp. 51–105.
Pasternak, C. A. (1987) Virus, toxin, complement: common actions and their prevention by Ca2+ or Zn2+.BioEssays 6:14–19.
Phillips, G. L. and Reece, D. E. (1986) Clinical studies of autologous bone marrow transplantation in Hodgkin's disease.Clin. Haematol. 15:151–166.
Piatek, M., Lane, J. A., Laird, W., Bjorn, M. J., Wang, A. and Williams, M. (1988) Expression of soluble and fully functional ricin A chain inEscherichia coli is temperatue-sensitive.J. Biol. Chem. 263:4837–4843.
Pimm, M. V., Jones, J. A., Price, M. R., Middle, J. G., Embleton, M. J. and Baldwin, R. W. (1982) Tumour localisation of monoclonal antibody against a rat mammary carcinoma and supression of tumour growth with adriamycin-antibody conjugates.Cancer Immunol. Immunotherapy 12:125–134.
Pirker, R., FitzGerald, D. J. P., Willingham, M. C. and Pastan, I. (1988) Enhancement of the activity of immunotoxins made with either ricin A chain orPseudomonas exotoxin in human ovarian and epidermoid carcinoma call lines.Cancer Res. 48:3919–3923.
Ramakrishnan, S. and Houston, L. (1984) Inhibition of human acute lymphoblastic leukaemia cells by immunotoxins: potentiation by chloroquine,Science 223:58–61.
Ramarkrishnan, S. and Houston, L. (1984) Prevention of growth of leukaemia cells in mice by monoclonal antibodies directed against thy 1.1 antigen disulfide linked to two ribosome inhibitors: pokeweed antiviral protein or ricin A chain.Cancer Res. 44:1398–1404.
Scott, C. F., Goldmacher, V. S., Lambert, J. M., Jackson, J. V. and McIntyre, G. D. (1987) An immunotoxin composed of a monoclonal antitransferrin receptor antibody linked by a disulphide bond to the ribosome-inactivating protein gelonin potentin vitro andin vivo effects against human tumors.J. Nat. Cancer Inst. 79:1163–1172.
Seto, M., Umemoto, N., Saito, M., Masuho, Y., Hara, T. and Takahashi, T. (1982) Monoclonal anti-MM46 antibody: ricin A chain conjugate:in vitro andin vivo antitumor activity.Cancer Res. 42:5209–5215.
Shen, G.-L., Li, J.-L., Ghetie, M.-A., Ghetie, V., May, R. D., Till, M., Brown, A. N., Relf, M., Knowles, P., Uhr, J. W., Janossy, G., Amlot, P., Vitetta, E. S. and Thorpe, P. E. (1988) Evaluation of four anti-CD 22 antibodies as ricin A chain-containing immunotoxins for thein vivo therapy of human B cell leukaemias and lymphomas.Int. J. Cancer 42:792–797.
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., 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 anti-melanoma antibody-ricin A chain immunotoxin.Cancer Res. 47:1717–1723.
Stirpe, F. and Barbieri, L. (1986) Ribosome-inactivating proteins up to date.FEBS Letts. 195:1–8.
Tai, J., Blair, A. H. and Ghose, T. (1979) Tumour inhibition by chlorambucil covalently linked to antitumour globulin.Eur J. Cancer 15:1357–1363.
Thorpe, P. E. (1985) Antibody carriers of cytotoxic agents in cancer therapy: a review. In:Monoclonal Antibodies '84:Biological and Clinical Applications, Pinchera, A., Doria, G., Dammacco, F. and Bargellesi, A., eds., pp. 475–506.
Thorpe, P. E., Ross, W. C. J., Brown, A. N. F., Myers, C. D., Cumber, A. J., Foxwell, B. M. J. and Forrester, J. T. (1984) Blockade of the galactose-binding sites of ricin by its linkage to antibody.Eur. J. Biochem. 140:63–71.
Thorpe, P. E., Blakey, D. C., Brown, A. N., Knowles, P. P., Knyba, R. E., Wallace, P. M., Watson, G. J. and Wawrzynczak, E. J. (1987) Comparison of two anti-thy 1.1 arbin A-chain immunotoxins prepared with different crosslinking agents: antitumour effects,in vivo fate, and tumor cell mutants.J. Natl. Cancer Inst. 79:1101–1112.
Thorpe, P. E., Brown, A. N., Bremmer, J. A., Foxwell, B. M. J. and Stirpe, F. (1985) An immunotoxin composed of monoclonal anti-thy 1.1 antibody and a ribosome-inactivating protein fromSaponaria officinalis: potent antitumor effectsin vitro andin vivo.J. Natl. Cancer Inst. 75:151–159.75:151–159.
Thorpe, P. E., Cumber, A. J., Williams, N., Edwards, D. C., Ross, W. C. J. and Davies, A. J. S. (1981) Abrogation of the non-specific toxicity of abrin conjugated to anti-lymphocyte globulin.Clin. Exp. Immunol. 43:195–200.
Thorpe, P. E., Wallace, P. M., Knowles, P. P., Relf, M. G., Brown, A. N., Watson, G. J., Knyba, R. E., Wawrzynczak, E. J. and Blakey, D. C. (1987a). New coupling agents for the synthesis of immunotoxins containing a hindered disulfide bond with improved stabilityin vivo.Cancer Res. 47:5924–5931.
Thorpe, P. E., Wallace, P. M., Knowles, P. P., Relf, M. G., Brown, A. N., Watson, G. J., Blakey, D. C. and Newell, D. R. (1988) Improved antitumor effects of immunotoxins prepared with deglycosylated ricin A-chain and hindered disulfide linkages.Cancer Res. 48:6396–6403.
Tsukada, Y., Hurwitz, E. and Kashi, R. (1982) Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat α-fetoprotein antibodies.Proc. Nat. Acad. Sci. (USA) 79:7896–7899.
Vitetta, E. S., Cushley, W. and Uhr, J. W. (1983) Synergy of ricin A chain-containing immunotoxins and ricin B chain-containing immunotoxins inin vitro killing of neoplastic human B cells.Proc. Nat. Acad. Sci. (USA) 80:6332–6335.
Vitetta, E. S., Fulton, R. J. and Uhr, J. W. (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.
Vogel, C.-W. and Muller-Eberhard, H. J. (1981) Induction of immune cytolysis: tumour-cell killing by complement is initiated by covalent complex of monoclonal antibody and stable C3/C5 convertase.Proc. Nat. Acad. Sci (USA) 78:7707–7711.
Vogel, C.-W., Wilkie, S. D. and Morgan, A. C. (1985)In vivo studies with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. In:Modern Trends in Human Leukaemia VI, Neth, R., Gallo, R. C., Greaves, M. F. and Janka, G., eds., Springer-Verlag, Berlin, pp. 514–517.
Von Wussow, P., Spitler, L., Block, B. and Deicher, H. (1988) Immunotherapy in patients with advanced malignant melanoma using a monoclonal anti-melanoma antibody ricin A immunotoxin.Eur. J. Cancer Clin. Oncol. 24:S69–73.
Ward, E. S., Ridley, A. R., Ellar, D. J. and Todd, J. A. (1986)Bacillus thuringiensis var.israelensis delta-endotoxin. Cloning and expression of the toxin in sporogenic and asporogenic strains ofBacillus subtillis.J. Mol. Biol. 191:13–22.
Wawrzynczak, E. J. and Thorpe, P. E. (1986) Monoclonal antibodies and therapy. In:Introduction to the Cellular and Molecular Biology of Cancer, Franks, L. M. and Teich, N. M., eds., Oxford University Press, pp. 378–410.
Wawrzynczak, E. J. and Thorpe, P. E. (1987) Methods for preparing immunotoxins: effect of the linkage on activity and stability. In:Immunoconjugates—Antibody Conjugates in Radioimaging and Therapy of Cancer, Vogel, C.-W., ed., Oxford University Press, pp. 28–55.
Youle, R. J. and Neville, D. M. (1980) Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell type specific toxin.Proc. Nat. Acad. Sci. (USA) 77:5483–5486.
Youle, R. J. and Neville, D. M. (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.
Zovickian, J. and Youle, R. J. (1988) Efficacy of intrathecal immunotoxin therapy in an animal model of leptomeningeal neoplasia.J. Neurosurg. 68:767–774.
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Drobniewski, F.A. Immunotoxins up to the present day. Biosci Rep 9, 139–156 (1989). https://doi.org/10.1007/BF01115993
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DOI: https://doi.org/10.1007/BF01115993