14
Views
0
CrossRef citations to date
0
Altmetric
Review

Recombinant toxins in haematologic malignancies and solid tumours

Pages 1405-1427 | Published online: 23 Feb 2005

Bibliography

  • LANDIS SH, MURRAY T, BOLDEN S, WINGO PA: Cancer statistics, 1998. CA Cancer I Clin. (1998) 48:6–29.
  • YAMAIZUMI M, MEKADA E, UCHIDA T, OKADA Y: One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell (1978) 15.245–250.
  • EIKLID K, OLSNES S, PIHL A: Entry of lethal doses of ab-rin, ricin and modeccin into the cytosol of HeLa cells. Exp. Cell Res. (1980) 126321–326.
  • CARROLL SF, COLLIER RJ: Active site of Pseudomonas aeruginosa exotoxin A. Glutamic acid 553 is photola-beled by NAD and shows functional homology with glutamic acid 148 of diphtheria toxin. J. Biol. Chem. (1987) 2628707–8711.
  • UCHIDA T, PAPPENHEIMER AM, JR., HARPER AA: Recon-stitution of diphtheria toxin from two nontoxic cross-reacting mutant proteins. Science (1972) 175:901–903.
  • UCHIDA T, PAPPENHEIMER AMJr, GREANY R: Diphtheria toxin and related proteins I. Isolation and properties of mutant proteins serologically related to diphtheria toxin. J. Biol. Chem. (1973) 248:3838–3844.
  • GLEWSKI BH, LIU PV, KABAT D: Mechanism of action ofPseudomonas earuginosa exotoxin A: Adenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo. Infect. Immun. (1977) 15:138–144.
  • VAN NESS BG, HOWARD JB, BODLEY JW: ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products. J. Biol. Chem. (1980) 255:10717–01720.
  • PHAN LD, PERENTESIS JP, BODLEY JW: Saccharomyces cerevisiae elongation factor 2. Mutagenesis of the histi-dine precursor of diphthamide yields a functional pro-tein that is resistant to diphtheria toxin. J. Biol. Chem. (1993) 268:8665–8668.
  • HWANG J, FITZGERALD DJ, ADHYA S, PASTAN I: Func-tional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell (1987) 48:129–136.
  • ALLURED VS, COLLIER RJ, CARROLL SF, MCKAY DB: Struc-ture of exotoxin A of Pseudomonas aeruginosa at 3.0 Angstrom resolution. Proc. Natl. Acad. Sci. USA (1986) 83:1320–1324.
  • HESSLER JL, KREITMAN RJ: An early step in Pseudomo-nas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor. Biochemistry (1997) 36:14577–14582.
  • KOUNNAS MZ, MORRIS RE, THOMPSON MR et al.: The a2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseu-domonas exotoxin A. J. Biol. Chem. (1 9 9 2) 267:12420–12423.
  • CHIRON MF, FRYLING CM, FITZGERALD DJ: Cleavage ofPseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. J. Biol. Chem. (1994) 269:18167–18176.
  • FRYLING C, OGATA M, FITZGERALD D: Characterizationof a cellular protease that cleaves Pseudomonas exo-toxin. Infect. Immun. (1992) 60:497–502.
  • OGATA M, FRYLING CM, PASTAN I, FITZGERALD DJ: Cell-mediated cleavage of Pseudomonas exotoxin be-tween Arg279 and G1y28° generates the enzymatically active fragment which translocates to the cytosol. Biol. Chem. (1992) 267:25396–25401.
  • CHAUDHARY VK, JINNO Y, FITZGERALD D, PASTAN I: Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxic-ity. Proc. Natl. Acad. Sci. USA (1990) 87:308–312.
  • KREITMAN RJ, PASTAN I: Importance of the glutamate residue of KDEL in increasing the cytotoxicity of Pseu-domonas exotoxin derivatives and for increased bind-ing to the KDEL receptor. Biochem. J. (1995) 307:29–37.
  • THEUER C, KASTURI S, PASTAN I: Domain II of Pseudo-monas exotoxin A arrests the transfer of translocating nascent chains into mammalian microsomes. Bio-chemistry (1994) 33:5894–5900.
  • THEUER CP, BUCHNER J, FITZGERALD D, PASTAN I: The N-terminal region of the 37-kDa translocated fragment of Pseudomonas exotoxin A aborts translocation by promoting its own export after microsomal mem-brane insertion. Proc. Natl. Acad. Sci. USA (1993) 90:7774–7778.
  • BRINKMANN U, BRINKMANN E, GALLO M, PASTAN I: Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSEL Proc. Natl. Acad. Sci. USA (1995) 92:10427–10431.
  • ROLF JM, GAUDIN HM, EIDELS L: Localization of thediphtheria toxin receptor-binding domain to the carboxyl-terminal Mr - 6000 region of the toxin. J. Biol. Chem. (1990) 265:7331–7337.
  • CHOE S, BENNETT MJ, FUJII G et al.: The crystal structure of diphtheria toxin. Science (1992) 357:216–222.
  • WILLIAMS DP, WEN Z, WATSON RS et al.: Cellular proc-essing of the interleukin-2 fusion toxin DAB486-IL-2 and efficient delivery of diphtheria fragment A to the cytosol of target cells requires Arg194. J. Biol. Chem. (1990) 265:20673–20677.
  • IWAMOTO R, HIGASHIYAMA S, MITAMURA T et al.: Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J (1994) 13:2322–2330.
  • VANDERSPEK J, CASSIDY D, GENBAUFFE F, HUYNH PD, MURPHY JR: An intact transmembrane helix 9 is essen-tial for the efficient delivery of the diphtheria toxin catalytic domain to the cytosol of target cells. J. Biol. Chem. (1994) 269:21455–21459.
  • ZHAN H, CHOE S, HUYNH PD eta].: Dynamic transitions of the transmembrane domain of diphtheria toxin: di-sulfide trapping and fluorescence proximity studies. Biochemistry (1994) 33:11254–11263.
  • CABIAUX V, MINDELL J, COLLIER RJ: Membrane translo-cation and channel-forming activities of diphtheria toxin are blocked by replacing isoleucine 364 with ly-sine. Infect. Immun. (1993) 61:2200–2202.
  • KAUL P, SILVERMAN J, SHEN WH et al.: Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein Science (1996) 5:687–692.
  • LEMICHEZ E, BOMSEL M, DEVILLIERS G et al: Membrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery. Mol. Mir-cobiol (1997) 23:445–457.
  • WILSON BA, BLANKE SR, REICH KA, COLLIER RJ: Active-site mutations of diphtheria toxin. Tryptophan 50 is a major determinant of NAD affinity. J. Biol. Chem. (1994) 269:23296–23301.
  • BENNETT MJ, EISENBERG D: Refined structure ofmonomeric diphtheria toxin at 2.3 A resolution. Pro-tein Science (1994) 3:1464–1475.
  • KONDO T, FITZGERALD D, CHAUDHARY VK, ADHYA S,PASTAN I: Activity of immunotoxins constructed with modified Pseudomonas exotoxin A lacking the cell recognition domain. J. Biol. Chem. (1988) 263:9470–9475.
  • WILLIAMS DP, PARKER K, BACHA P, BISHAI W, BOR-OWSKI M et al.: Diphtheria toxin receptor binding do-main substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein. Protein Eng. (1987) 1:493–498.
  • SIEGALL CB, CHAUDHARY VK, FITZGERALD DJ, PASTAN I: Functional analysis of domains II, Ib, and III of Pseu-domonas exotoxin. J. Biol. Chem. (1989) 264:14256–14261.
  • KREITMAN RJ, BATRA JK, SEETHARAM S et al.: Single-chain immunotoxin fusions between anti-Tac and Pseudomonas exotoxin: relative importance of the two toxin disulfide bonds. Bioconjugate Chemistry (1993) 4:112–120.
  • WILLIAMS DP, SNIDER CE, STROM TB, MURPHY JR: Struc-ture/function analysis of interleukin-2-toxin (DAB486-11-2). Fragment B sequences required for the delivery of fragment A to the cytosol of target cells. J. Biol. Chem. (1990) 265:11885–11889.
  • CHAUDHARY VK, FITZGERALD DJ, PASTAN I: A proper amino terminus of diphtheria toxin is important for cytotoxicity. Biochem. Biophys. Res. Commun. (1991) 180:545–551.
  • SEETHARAM S, CHAUDHARY VK, FITZGERALD D, PAS-TAN I: Increased cytotoxic activity of Pseudomonas exotoxin and two chimeric toxins ending in KDEL. J. Biol. Chem. (1991) 266:17376–17381.
  • ENDO Y, MITSUI K, MOTIZUKI M, TSURUGI K: The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. J. Biol. Chem. (1987) 262:5908–5912.
  • ZAMBONI M, BRIGOTTI M, RAMBELLI F, MONTANARO L, SPERTI S: High pressure liquid chromatographic and fluorimetric methods for the determination of ade-nine released from ribosomes by ricin and gelonin. Biochem. J. (1989) 259:639–643.
  • MOHANRAJ D, RAMAKRISHNAN S: Cytotoxic effects of ricin without an interchain disulfide bond: genetic modification and chemical crosslinking studies. Bio-chim. Biophys. Acta (1995) 1243:399–406.
  • RAMAKRISHNAN S, BJORN MJ, HOUSTON LL: Recombi-nant ricin A chain conjugated to monoclonal antibod-ies: improved tumor cell inhibition in the presence of lysosomotropic compounds. Cancer Res. (1989) 49:613–7.
  • KREITMAN RJ: Getting plant toxins to fuse. leukaemiaRes. (1997) 21:997–999.
  • FRANKEL AE, BURBAGE C, FU T et al: Ricin toxin con-tains at least three galactose-binding sites located in B chain subdomains 1 alpha, 1 beta, and 2 gamma. Bio-chemistry (1996) 35:14749–14756.
  • FRANKEL AE, BURBAGE C, FU T et al: Characterization of a ricin fusion toxin targeted to the interleukin-2 re-ceptor. Protein Eng. (1996) 9:913–919.
  • FRANKEL A, TAGGE E, CHANDLER J et al: 112-ricin fu-sion toxin is selectively cytotoxic in vitro to IL2 receptor-bearing tumor cells. Bioconjugate Chemistry (1995) 6:666–672.
  • KREK CE, LADINO CA, GOLDMACHER VS, BLATTLER WA, GUILD BC: Expression and secretion of a recombinant ricin immunotoxin from murine myeloma cells. Pro-tein Eng. (1995) 8:481–489.
  • TANIGUCHI T, MINAMI Y: The 112/11-2 receptor system: a current overview. Cell (1993) 73:5–8.
  • KODAKA T, UCHIYAMA T, ISHIKAWA T et al.: Interleukin-2 receptor b-chain (p70-75) expressed on leukemic cells from adult T cell leukaemia patients. Jpn. J. Cancer Res. (1990) 81:902–908.
  • YAGURA H, TAMAKI T, FURITSU T et al.: Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukaemia cells: functional and struc-tural characterization. Blut (1990) 60:181–186.
  • KREITMAN RJ, PASTAN I: Recombinant single-chain im-munotoxins against T and B cell leukaemias. Leuk. Lym-phoma (1994) 13:1–10.
  • ROBB RJ, GREENE WC, RUSK CM: Low and high affinity cellular receptors for interleukin 2. J. Exp. Med. (1984) 160:1126–1146.
  • GAZZOLA M, COLLINS NH, TAFURI A, KEEVER CA: Re-combinant interleukin 3 induces interleukin 2 recep-tor expression on early myeloid cells in normal human bone marrow. Exp. Hematol. (1992) 20:201–208.
  • HOSHINO S, OSHIMI K, MIZOGUCHI H: Interleukin-2 re-ceptor b chain in leukaemias and lymphomas. Leuk. & lymphoma (1992) 6:107–116.
  • BACHA P, WILLIAMS DP, WATERS C et al.: Interleukin 2 receptor-targeted cytotoxicity: interleukin 2 receptor-mediated action of a diphtheria toxin-related inter-leukin 2 fusion protein. J. Exp. Med. (1988) 167:612–622.
  • LORBERBOUM-GALSKI H, FITZGERALD D, CHAUDHARY V, ADHYA S, PASTAN I: Cytotoxic activity of an inter-leukin 2-Pseudomonas exotoxin chimeric protein produced in Escherichia colt'. Proc. Natl. Acad. ScL USA (1988) 85:1922-1926. © Ashley Publications Ltd. All rights reserved.Exp. Opin. Invest. Drugs (1998) 7(9)
  • LORBERBOUM-GALSKI H, KOZAK RW, WALDMANN TA etInterleukin 2 0121 PE40 is cytotoxic to cells dis-playing either the p55 or p70 subunit of the 112 recep-tor. J. Biol. Chem. (1988) 263:18650–18656.
  • WATERS CA, SCHIMKE PA, SNIDER CE etal.: Interleukin 2receptor-targeted cytotoxicity. Receptor binding re-quirements for entery of a diphtheria toxin-related in-terleukin 2 fusion protein into cells. Eur. J. Immunol. (1990) 20:785–791.
  • RE GG, WATERS C, POISSON L et al: Interleukin 2 (11-2)receptor expression and sensitivity to diphtheria fu-sion toxin DAB(389)IL-2 in cultured hematopoietic cells. Cancer Res. (1996) 56:2590–2595.
  • LORBERBOUM-GALSKI H, GARSIA RJ, GATELY M et al:112-PE664Giu, a new chimeric protein cytotoxic to hu-man activated T lymphocytes. J. Biol. Chem. (1990) 265:16311–16317.
  • LORBERBOUM-GALSKI H, BARRETT LV, KIRKMAN RL etal: Cardiac allograft survival in mice treated with 11-2-PE40. Proc. Natl. Acad. ScL USA (1989) 86:1008–1012.
  • LORBERBOUM-GALSKI H, LAFYATIS R, CASE JP et al.: Ad-ministration of 11-2-PE40 via osmotic pumps prevents adjuvant induced arthritis in rats. Improved therapeu-tic index of 11-2-PE40 administered by continuous in-fusion. Intl. J. Immunopharmac. (1991) 13:305–315.
  • KELLEY VE, BACHA P, PANKEWYCZ 0 et al: Interleukin2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo. Proc. Natl. Acad. ScL USA (1988) 85:3980–3984.
  • BACHA PA, FORTE SE, MCCARTHY DM et al: Impact ofinterleukin-2-receptor-targeted cytotoxins on a unique model of murine interleukin-2-receptor-expressing malignancy. Int. J. Cancer (1991) 49:96–101.
  • MACKIE JD, PANKEWYCZ OG, HASSARJIAN R et al.: Im-munotherapy using interleukin-2 diphtheria toxin chimer prolongs murine allografts. Transplant Proc. (1989) 21:2718–2719.
  • KIRKMAN RL, BACHA P, BARRETT LV et al.: Prolongationof cardiac allograft survival in murine recipients treated with a diphtheria toxin-related interleukin-2 fusion protein. Transplantation (1989) 47:327–330.
  • PANKEWYCZ 0, MACKIE J, HASSARJIAN R et al.:Interleukin-2-diphtheria toxin fusion protein pro-longs murine islet cell engraftment. Transplantation (1989) 47:318–322.
  • MILLER DD, BACH RG, TIO FO et al: Interleukin-2receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis. Atherosclerosis (1996) 126:1–14.
  • ROSE JW, LORBERBOUM-GALSKI H, FITZGERALD D et al:Chimeric cytotoxin 112-PE40 inhibits relapsing ex-perimental allergic encephalomyelitis. J. Neuroimmu-nol. (1991) 32:209–217.
  • HERBORT CP, SMET MDD, ROBERGE FG et al.: Treatmentof corneal allograft rejection with the cytotoxin 11-2 - PE40. Transplantation (1991) 52:470–474.
  • KOZAK RW, LOBERBOUM-GALSKI H, JONES L et al.: 11-2-PE40 prevents the development of tumors in mice in-jected with 11-2 receptor expressing EL4 transfectant tumor cells. J. Immunol (1990) 145:2766–2771.
  • CASE JP, LORBERBOUM-GALSKI H et al.: Chimeric cyto-toxin 112-PE40 delays and mitigates adjuvant-induced arthritis in rats. Proc. Natl. Acad. Sci. USA (1989) 86:287–291.
  • HULLETT DA, LANDRY AS, ECKHOFF DE et al.: DAB486-11-2 (11-2-toxin) in combination with low-dose RS-61443 (mycophenolate mofetifi prolongs murine thy-roid allograft survival. Transplant. Proc. (1993) 25:756–7.
  • PURI RK, FITZGERALD D, LELAND P, KOZAK RW, PASTANI: In vitro and in vivo suppression of interleukin-2-activated killer cell activity by chimeric proteins be-tween interleukin-2 and Pseudomonas exotoxin. Cell Immunol. (1992) 143:324–34.
  • WALZ G, ZANKER B, BRAND K et al: Sequential effects ofinterleukin 2-diphtheria toxin fusion protein on T-cell activation. Proc. Natl. Acad. Sci. USA (1989) 86:9485–8.
  • LEMAISTRE CF, ROSENBLUM MG, REUBEN JM et al.: Therapeutic effects of genetically engineered toxin (DAB48611-2) in patient with chronic lymphocytic leu-kaemia. Lancet (1991) 337:1124–1125.
  • LEMAISTRE CF, MENEGHETTI C, ROSENBLUM M et al.:Phase I trial of an interleukin-2 01-21 fusion toxin (DAB48611-2) in hematologic malignancies expressing the 11-2 receptor. Blood (1992) 79:2547–2554.
  • LEMAISTRE CF, CRAIG FE, MENEGHETTI C et al.: Phase Itrial of a 90-minute infusion of the fusion toxin DAB48611.-2 in hematological cancers. Cancer Res. (1993) 53:3930–3934.
  • KUZEL TM, ROSEN ST, GORDON LI et al.: Phase I trial ofthe diphtheria toxin/interleukin-2 fusion protein DAB486IL-2: efficacy in mycosis ftmgoides and other non-Hodgkin's lymphomas. Leuk. and Lymphoma (1993) 11:369–377.
  • HESKETH P, CAGUIOA P, KOH H, DEWEY H, FACADA A etal.: Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma. J. Clin. Oncol (1993) 11:1682–1690.
  • TEPLER I, SCHWARTZ G, PARKER K, CHARETTE J, KADINME et al.: Phase I trial of an interleukin-2 fusion toxin (DAB48611-2) in hematologic malignancies: Complete response in a patient with Hodgkin's disease refrac-tory to chemotherapy. Cancer (1994) 73:1276–1285.
  • PLATANIAS LC, RATAIN MJ, SOB, LARSON RA, VARDIMANJW et al.: Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB48611-2) as a 6 hour in-travenous infusion in patients with hematologic ma-lignancies. Leuk. Lymphoma (1994) 14:257–262.
  • COHEN R, JAFFE ES, STETLER-STEVENSON MA et al: Bilat-eral adrenal hemorrhage and adrenal insufficiency in a patient with lymphomatous adrenal infiltration fol-lowing administration of a fusion toxin (DAB486 interleukin-2). J. Immunother. Emphasis Tumour. Immu-nol. (1994) 16.229–233.
  • FOSS FM, BORKOWSKI TA, GILLIOM M eta].: Chimeric fu-sion protein toxin DAB486IL-2 in advanced mycosis ftmgoides and the sezary syndrome: correlation of ac-tivity and interleukin-2 receptor expression in a phase II study. Blood (1994) 84:1765–1774.
  • SEWELL KL, PARKER KC, WOODWORTH TG et al.: DAB486IL-2 fusion toxin in refractory rheumatoid ar-thritis. Arthritis Rheum. (1993) 36:1223–1233.
  • MORELAND LW, SEWELL KL, TRENTHAM DE et al.: Interleukin-2 diphtheria fusion protein (DAB(486)I1-2) in refractory rheumatoid arthritis: A double-blind, placebo-controlled trial with open-label extension. Arthritis Rheum. (1995) 38:1177–1186.
  • LEMAISTRE CF, SALEH MN, KUZEL TM et al.: Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood (1998) 91:399–405.
  • WALDMANN TA, GOLDMAN CK, ROBB RJ et al: Expres-sion of interleukin 2 receptors on activated human B cells. J. Exp. Med. (1984) 160:1450–1466.
  • HUSTON JS, LEVINSON D, MUDGETT-HUNTER M et al.: Protein engineering of antibody binding sites: Recov-ery of specific activity in an antidigoxin single-chain Fv analogue produced in Escherichia coil Proc. Natl. Acad. Sci. USA (1988) 85:5879–5883.
  • BIRD RE, HARDMAN KD, JACOBSON JW et al: Single-chain antigen-binding proteins. Science (1988) 242:423–426.
  • CHAUDHARY VK, QUEEN C, JUNGHANS RP, WALDMANN TA, FITZGERALD DJ eta].: A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature (1989) 339:394–397.
  • BATRA JK, FITZGERALD D, GATELY M, CHAUDHARY VK, PASTAN I: Anti-Tac(Fv)-PE40: a single chain antibody Pseudomonas fusion protein directed at interleukin 2 receptor bearing cells. J. Biol. Chem. (1990) 265:15198–15202.
  • KREITMAN RJ, CHAUDHARY VK, WALDMANN T, WILLINGHAM MC, FITZGERALD DJ et al.: The recombi-nant immunotoxin and-Tac(Fv)-Pseuodomonas exo-toxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukae-mia. Proc. Natl. Acad. ScL USA (1990) 87:8291–8295.
  • KREITMAN RJ, CHAUDHARY VK, WALDMANN TA, HAN-CHARD B, CRANSTON B et al.: Cytotoxic activities of re-combinant immunotoxins composed of Pseudomonas toxin or diphtheria toxin toward lym-phocytes from patients with adult T-cell leukaemia. Leukaemia (1993) 7:553–562.
  • SAITO T, KREITMAN RJ, HANADA S-I, MAKINO T, UT-SUNOMIYA A et al.: Cytotoxicity of recombinant Fab and Fv immunotoxins on adult T-cell leukaemia lymph node and blood cells in the presence of soluble interleukin-2 receptor. CancerRes. (1994) 54:1059–1064.
  • KIYOKAWA T, SHIRONO K, HATTORI T et al.: Cytotoxic-ity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukaemia. Cancer Res. (1989) 49:4042–4046.
  • KREITMAN RJ, BAILON P, CHAUDHARY VK, FITZGERALD DJP, PASTAN I: Recombinant immunotoxins contain-ing anti-Tac(Fv) and derivatives of Pseudomonas exo-toxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma. Blood (1994) 83:426–434.
  • KREITMAN RJ, PASTAN I: Targeting Pseudomonas exo-toxin to hematologic malignancies. Semin. Cancer. Biol. (1995) 6:297–306.
  • KREITMAN RJ, PASTAN I: Accumulation of a recombi-nant immunotoxin in viva less than 1000 molecules per cell is sufficient for complete responses. Cancer Res. (1998) 58:968–975.
  • DE GAST GC, GRATAMA JW, VERDONCK LF et al.: The in-fluence of T cell depletion on recovery of T cell prolif-eration to herpesviruses and Candida after allogeneic bone marrow transplantation. Transplantation (1989) 48:111–115.
  • HERTENSTEIN B, HAMPL W, BUNJES D et al.: In vivo/ex vivo T cell depletion for GVHD prophylaxis influences onset and course of active cytomegalovirus infection and disease after BMT. Bone Marrow Transplant. (1995) 15:387–393.
  • MAVROUDIS DA, JIANG YZ, HENSEL N et al: Specific de-pletion of alloreactivity against haplotype mis-matched related individuals: a new approach to graft-versus-host disease prophylaxis in haploidenti-cal bone marrow transplantation. Bone Marrow Trans-plant. (1996) 17:793–799.
  • REITER Y, BRINKMANN U, KREITMAN RJ eta].: Stabiliza-tion of the Fv fragments in recombinant immunotox-ins by disulfide bonds engineered into conserved framework regions. Biochemistry (1994) 33:5451–5459.
  • REITER Y, KREITMAN RJ, BRINKMANN U, PASTAN I: Cyto-toxic and antitumor activity of a recombinant immu-notoxin composed of disulfide-stablized anti-Tac Fv fragment and truncated Pseudomonas exotoxin. Int. J. Cancer (1994) 58:142–149.
  • ENGERT A, MARTIN G, AMLOT P et al.: Immunotoxins constructed with anti-CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent anti-tumour effects against human Hodgkin cells in vitro and solid Hodgkin tumours in mice. Int. J. Cancer (1991) 49:450–456.
  • ENGERT A, GOTTSTEIN C, WINKLER U et al. Experimen- tal treatment of human Hodgkin's disease with ricin A-chain immunotoxins. Leuk. Lymphoma (1994) 13:441–448.
  • WINKLER U, GOTTSTEIN C, SCHON G et al: Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immu-notoxins. Blood (1994) 83:466–475.
  • ENGERT A, DIEHL V, SCHNELL R et al.: A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lym-phoma. Blood (1997) 89:403–410.
  • BARTH S, HUHN M, WELS W, DIEHL V, ENGERT A: Con-struction and in vitro evaluation of RFT5(scFv)-ETA', a new recombinant single-chain immunotoxin with specific cytotoxicity toward CD25+ Hodgkin-derived cell lines. Int. J. Molec. Med. (1998) 1:249–256.
  • WELS W, HARWERTH I-M, MUELLER M, GRONER B, HY-NES NE: Selective inhibition of tumor cell growth by a recombinant single-chain antibody-toxin specific for the erbB-2 receptor. Cancer Res. (1992) 52:6310–6317.
  • KREITMAN RJ, SCHNEIDER WP, QUEEN C et al: Mik-bl (Fv)-PE40, a recombinant immunotoxin cytotoxic toward cells bearing the b-chain of the IL-2 receptor. J. Immunol. (1992) 149:2810–2815.
  • LAW CL, ARUFFO A, CHANDRAN KA, DOTY RT, CLARK EA: Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind multiple sialylated ligands expressed on B and T cells. J. Immunol (1995) 155:3368–3376.
  • OTIPOBY KL, ANDERSSON KB, DRAVES KE et al: CD22 regulates thymus-independent responses and the life-span of B cells. Nature (1996) 384:634–637.
  • GHETIE M-A, TUCKER K, RICHARDSON J, UHR JW, VITETTA ES: The antitumor activity of an anti-CD22 im-munotoxin in SCID mice with disseminated Daudi lymphoma is enhanced by either an anti-CD19 anti-body or an anti-CD19 immunotoxin. Blood (1992) 80:2315–2320.
  • AMLOT PL, STONE MJ, CUNNINGHAM D et al.: A phase I study of an anti-CD22-deglycosylated ricin A chain im-munotoxin in the treatment of B-cell lymphomas re-sistant to conventional therapy. Blood (1993) 82:2624–2633.
  • VITETTA ES, STONE M, AMLOT P et al.: Phase I immuno-toxin trial in patients with B-cell lymphoma. Cancer Res. (1991) 51:4052–4058.
  • MANSFIELD E, PASTAN I, FITZGERALD DJ: Characteriza-tion of RFB4-Pseudomonas exotoxin A immunotoxins targeted to CD22 on B-cell malignancies. Bioconjug. Chem. (1996) 7:557–563.
  • KREITMAN RJ, HANSEN HJ, JONES AL et al.: Pseudomo-nas exotoxin-based immunotoxins containing the an-tibody LL2 or LL2-Fab' induce regression of subcutaneous human B-cell lymphoma in mice. Can-cer Res. (1993) 53:819–825.
  • THEUER CP, KREITMAN RJ, FITZGERALD DJ, PASTAN I: Immunotoxins made with a recombinant form of Pseudomonas exotoxin A that do not require prote-olysis for activity. Cancer Res. (1993) 53:340–347.
  • MANSFIELD E, CHIRON MF, AMLOT P, PASTAN I, FITZGERALD DJ: Recombinant RFB4 single-chain im-munotoxin that is cytotoxic towards CD22-positive cells. Biochem. Soc. Trans. (1997) in press.
  • MANSFIELD E, AMLOT P, PASTAN I, FITZGERALD DJ: Re-combinant RFB4 immunotoxins exhibit potent cyto-toxic activity for CD22-bearing cells and tumors. Blood (1997) 90: 2020-2026.
  • VALLERA DA, PANOSKALTSIS-MORTARI A, JOST C et al.: Anti-graft- versus-host disease effect of DT390-anti--CD3sFv, a single-chain Fv fusion immunotoxin spe-cifically targeting the CD3e moiety of the T-cell receptor. Blood (1996) 88:2342–2353.
  • VALLERA DA, PANOSKALTSIS-MORTARI A, BLAZAR BR: Renal dysfunction accounts for the dose limiting toxic-ity of DT390anti-CD3sFv, a potential new recombinant anti-GVHD immunotoxin. Protein Eng. (1997) 10:1071–6.
  • MA S, HUH, THOMPSON J, STAVROU S et al.: Genetic con-struction and characterization of an anti-monkey CD3 single-chain immunotoxin with a truncated diphthe-ria toxin. Bioconjug. Chem. (1997) 8:695–701.
  • KAWANO M, HIRANO T, MATSUDA T et al.: Autocrine generation and requirement of BSF-2/11-6 for human multiple myelomas. Nature (1988) 332:83–85.
  • SIEGALL CB, SCHWAB G, NORDAN RP, FITZGERALD DJ, PASTAN I: Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. Cancer Res. (1990) 50:7786–7788.
  • SIEGALL CB, FITZGERALD DJ, PASTAN I: Cytotoxicity of 116-PE40 and derivatives on tumor cells expressing a range of interleukin 6 receptor levels. J. Biol. Chem. (1990) 265:16318–16323.
  • SIEGALL CB, NORDAN RP, FITZGERALD DJ, PASTAN I: Cell-specific toxicity of a chimeric protein composed of interleukin-6 and Pseudomonas exotoxin (16-PE40) on tumor cells. Mol Cell. Biol. (1990) 10:2443–2447.
  • SIEGALL CB, KREITMAN RJ, FITZGERALD DJ, PASTAN I: Antitumor effects of interleukin 6-Pseudomonas exo-toxin chimeric molecules against the human hepato-cellular carcinoma, PLC/PRF/5 in mice. Cancer Res. (1991) 51:2831–2836.
  • ROZEMULLER H, ROMBOUTS WJC, TOUW IP et al.: Treat-ment of acute myelocytic leukaemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukae-mia model. leukaemia (1996) 10: 1796-1803.
  • CHADWICK DE, JEAN LF, JAMAL N et al: Differential sen-sitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diph-theria toxin-interleukin 6 fusion protein. Br. J. Haema-tol (1993) 85:25–36.
  • JEAN L-FL, MURPHY JR: Diphtheria toxin receptor-binding domain substitution with interleukin-6: Ge-netic construction and interleukin 6 receptor-specific action of a diphtheria toxin-related interleukin 6 fu-sion protein. Protein Eng. (1991) 4:989–994.
  • MORISAKI T, YUZUKI DH, UN RT et al.: Interleukin 4 re-ceptor expression and growth inhibition of gastric carcinoma cells by interleukin 4. Cancer Res. (1992) 52:6059–6065.
  • TOPP MS, KOENIGSMANN M, ANTHONY M et al.: Recom-binant human interleukin-4 inhibits growth of some human lung tumor cell lines in vitro and in vivo. Blood (1993) 82:2837–2844.
  • TOT M, BICKNELL R, HARRIS AL: Inhibition of colon and breast carcinoma cell growth by interleukin-4. Cancer Res. (1992) 52:275–279.
  • HOON DSB, BANEZ M, OKUN E, MORTON DL, IRIE RF: Modulation of human melanoma cells by interleukin-4 and in combination with g-interferon or a-tumor ne-crosis factor. Cancer Res. (1991) 51:2002–2008.
  • OBIRI NI, HILLMAN GG, HAAS GP, SUD S, PURI RK: Ex-pression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tu-mor cell growth in vitro by interleukin-4. J. Clin. Invest. (1993) 91:88–93.
  • OBIRI NI, SIEGEL JP, VARRICCHIO F, PURI RK: Expres-sion of high-affinity IL-4 receptors on human mela-noma, ovarian and breast carcinoma cells. Clin. Exp. Immunol. (1994) 95:148–155.
  • PURI RK, DEBINSKI W, OBIRI N, KREITMAN R, PASTAN I: Human renal cell carcinoma cells are sensitive to the cytotoxic effect of a chimeric protein composed of hu-man interleukin-4 and Pseudomonas exotoxin. Immunol. (1994) 154:369–379.
  • VARRICCHIO F, OBIRI NI, HAAS GP, PURI RK: Immu-nostaining of interleukin-4 receptor on human renal cell carcinoma. Lymphokine Cytokine Res. (1993) 12:465–469.
  • PURI RK, LELAND P, KREITMAN RJ, PASTAN I: Human neurological cancer cells express interleukin-4 (11-4) receptors which are targets for the toxic effects of 1L4-Pseudomonas exotoxin chimeric protein. Int. J. Cancer (1994) 58:574–581.
  • MORI N, YAMASHITA U, TANAKA Y et al.: Interleukin-4 induces proliferation of adult T-cell leukaemia cells. Eur. Haematol. (1993) 50:133–140.
  • MORI N, SHIRAKAWA F, MURAKAMI S, ODA S, ETO S: In-hibitory effect of interleukin 4 on production of inter-leukin 6 by adult T-cell leukaemia cells. Cancer Res. (1993) 53:4643–4647.
  • HUSAIN SR, GILL P, KREITMAN RJ, PASTAN I, PURI RK Interleukin-4 receptor expression on AIDS-associated Kaposi's sarcoma cells and their targeting by a chi-meric protein comprised of circularly permuted 11-4 and Pseudomonas exotoxin. Molecular Medicine (1997) 3:327–338.
  • DEBINSKI W, PURI RK, KREITMAN RJ, PASTAN I: A wide range of human cancers express interleukin 4 (14) re-ceptors that can be targeted with chimeric toxin com-posed of IL4 and Pseudomonas exotoxin. J. Biol. Chem. (1993) 268:14065–14070.
  • DEBINSKI W, PURI RK, PASTAN I: Interleukin-4 recep-tors expressed on tumors may serve as a target for anticancer therapy using chimeric Pseudomonas exo-toxin. Int. J. Cancer (1994) 58:744–748.
  • PURI RK, MEHROTRA PT, LELAND P et al.: A chimeric pro-tein comprised of 11-4 and Pseudomonas exotoxin is cytotoxic for activated human lymphocytes. J. Immu-nol (1994) 152:3693–3700.
  • JABARA HH, VERCELLI D, SCHNEIDER LC et al.: Interleukin-4 receptor expression by human B cells: Functional alalysis with a human interleukin-4 toxin, DAB38911-4. J. Allergy Clin. Immunol. (1995) 95:893–900.
  • CAI J, ZHENG T, MURPHY J, WATERS CA, LIN GY et al.: IL-4R expression in AIDS-KS cells and response to rhIL-4 and 11-4 toxin (DAB389-IL-4). Invest. New Drugs (1997) 15:279–287.
  • LE HV, SEELIG GF, SYTO R et al.: Selective proteolytic cleavage of recombinant human interleukin 4. Evi-dence for a critical role of the C-terminus. Biochemistry (1991) 30:9576–9582.
  • RAMANATHAN L, INGRAM R, SULLIVAN L eta].: Immuno-chemical mapping of domains in human interleukin 4 recognized by neutralizing monoclonal antibodies. Biochemistry (1993) 32:3549–3556.
  • POWERS R, GARRETT DS, MARCH CJ et al.: Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. Science (1992) 256: 1673-1677.
  • POWERS R, GARRETT DS, MARCH CJ et al.: The high-resolution, three-dimensional solution structure of human interleukin-4 determined by multidimen-sional heteronuclear magnetic resonance spectros-copy. Biochemistry (1993) 32:6744–6762.
  • MORRISON BW, LEDER P: A receptor binding domain of mouse interleukin-4 defined by a solid-phase binding assay and in vitro mutagenesis. J. Biol. Chem. (1992) 267:11957–11963.
  • WALTER MR, COOK WJ, ZHAO BG et al.: Crystal structure of recombinant human interleukin-4. J. Biol. Chem. (1992) 267:20371–20376.
  • KREITMAN RJ, PURI RK, PASTAN I: A circularly permuted recombinant interleukin 4 toxin with increased activ-ity. Proc. Natl. Acad. Sci. USA (1994) 91:6889–6893.
  • KREITMAN RJ, PURI RK, LELAND P, LEE B, PASTAN I: Site-specific conjugation to interleukin 4 containing mu-tated cysteine residues produces interleukin 4-toxin conjugates with improved binding and activity. Bio-chemistry (1994) 33: 11637-11644.
  • KREITMAN RJ, PURI RK, PASTAN I: Increased antitumor activity of a circularly permuted interleukin 4-toxin in mice with interleukin 4 receptor-bearing human carci-noma. Cancer Res. (1995) 55:3357–3363.
  • PURI RK, HOON DS, LELAND P etal.: Preclinical develop-ment of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Can-cer Res. (1996) 56:5631–5637.
  • YOULE RJ: Immunotoxins for central nervous system malignancy. Semin. Cancer Biol. (1996) 7:65–70.
  • RIEDEL CJ, MURASZKO KM, YOULE RJ: Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons. Proc. Natl. Acad. ScL USA (1990) 87:5051–5055.
  • WOGNUM AW, WESTERMAN Y, VISSER TP, WAGEMAKER G: Distribution of receptors for granulocyte-macrophage colony-stimulating factor on immature CD34+ bone marrow cells, differentiating monomye-loid progenitors, and mature blood cell subsets. Blood (1994) 84:764–774.
  • CHIBA S, SHIBUYA K, PIAO Y et al.: Identification and cellular distribution of distinct proteins forming hu-man GM-CSF receptor. Cell Regulation (1990) 1:327–335.
  • BERDEL WE, DANHAUSER-RIEDL S, STEINHAUSER G, WINTON EF: Various hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of non-hematopoietic tumor cells. Blood (1989) 73:80–83.
  • BALDWIN GC, GASSON JC, KAUFMAN SE et al.: Nonhe-matopoietic tumor cells express functional GM-CSF re-ceptors. Blood (1989) 73:1033–1037.
  • DIPPOLD WG, KLINGEL R, KERLIN M, SCHWAEBLE W, BUSCHENFELDE KMZ: Stimulation of pancreas and gas-tric carcinoma cell growth by interleukin 3 and granulocyte-macrophage colony stimulating factor. Gastroenterology (1991) 100,1338–1344.
  • HIRSCH T, EGGSTEIN S, FRANK S, FARTHMANN EH, SPECHT BV: Expression of GM-CSF and a functional GM-CSF receptor in the human colon carcinoma line SW403. Biochem. Biophys. Res. Comm. (1995) 217:138–143.
  • TOJO A, OSHIMA Y: [Targeted toxin therapy in the treat-ment of leukaemia]. Rinsho Ketsueki (1995) 36:578–81.
  • CHADWICK DE, WILLIAMS DP, NIHO Y, MURPHY JR, MIN-DEN MD: Cytotoxicity of a recombinant diphtheria toxin-granulocyte colony-stimulating factor fusion protein on human leukemic blast cells. Leuk. Lym-phoma (1993) 11:249–262.
  • KREITMAN RJ, PASTAN I: Recombinant toxins contain-ing human granulocyte-macrophage colony-stimulating factor and either Pseudomonas exotoxin or diphtheria toxin kill gastrointestinal cancer and leukaemia cells. Blood (1997) 90:252–259.
  • PERENTESIS JP, WADDICK KG, BENDEL AE et al.: Induc-tion of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukaemia cells by a recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor re-ceptor. Clinical Cancer Research (1997) 3:347–355.
  • BENDEL AE, SHAO Y, DAVIES SM et al.: A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor. leukaemia & Lym-phoma (1997) 25:257.
  • FRANKEL AE, HALL PD, BURBAGE C et al: Modulation of the apoptotic response of human myeloid leukaemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein. Blood (1997) 90:3654–3661.
  • PERENTESIS JP, BENDEL AE, SHAO Y et al.: Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukaemias. leukaemia & Lym-phoma (1997) 25:247.
  • ROZEMULLER H, ROMBOUTS EJC, TOUW IP et al.: Sensi-tivity of human acute myeloid leukaemia to diphtheria toxin-GM-CSF fusion protein. Br. J. Haematol. (1997) 98:952–959.
  • TERPSTRA W, ROZEMULLER H, BREEMS DA et al.: Diph-theria toxin fused to granulocyte-macrophage colony-stimulating factor eliminates acute myeloid leukaemia cells with the potential to initiate leukaemia in immunodeficient mice, but spares normal hemato-poietic stem cells. Blood (1997) 90:3735–3742.
  • PERENTESIS JP, GUNTHER R, WAURZYNIAK B et al.: In vivo biotherapy of HL-60 myeloid leukaemia with a ge-netically engineered recombinant fusion toxin di-rected against the human granulocyte macrophage colony-stimulating factor receptor. Clin. Cancer Res. (1997) 3:2217–2227.
  • ROZEMULLER H, ROMBOUTS EJC, TOUW IP et al.: In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF. leukaemia (1998) 12:710–717.
  • LEDBETTER JA, SHU G, GALLAGHER M, CLARK EA: Aug-mentation of normal and malignant B cell prolifera-tion by monoclonal antibody to the B cell-specific antigen BP50 (CDW40). J. Immunol (1987) 138:788–94.
  • FRANCISCO JA, GILLILAND LK, STEBBINS MR et al.: Activ-ity of a single-chain immunotoxin that selectively kills lymphoma and other B-lineage cells expressing the CD40 antigen. Cancer Res. (1995) 55:3099–3104.
  • FRANCISCO JA, SCHREIBER GJ, COMERESKI CR et al.: In vivo efficacy and toxicity of a single-chain immuno-toxin targeted to CD40. Blood (1997) 89:4493–500.
  • FRANCISCO JA, GAWLAK SL, SIEGALL CB: 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 (1997) 272:24165–24169.
  • FRANCISCO JA, GAWLAK SL, MILLER M et al.: Expression and characterization of bryodin 1 and a bryodin 1-based single-chain immunotoxin from tobacco cell culture. Bioconjug. Chem (1997) 8:708–713.
  • PLESNER T, BEHRENDT N, PLOUG M: Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR. Stem Cells (1997) 15:398–408.
  • CAVALLARO U, DEL VECCHIO A, LAPPI DA, SORIA MR: A conjugate between human urokinase and saporin, a type-1 ribosome-inactivating protein, is selectively cy-totoxic to urokinase receptor-expressing cells. J. Biol. Chem. (1993) 268:23186–23190.
  • 18CAVALLARO U, SORIA MR: Targeting plant toxins to the urokinase and alpha 2-macroglobulin receptors. Semin. Cancer Biol. (1995) 6:269–278.
  • FABBRINI MS, CARPANI D, BELLO-RIVERO I, SORIA MR: The amino-terminal fragment of human urokinase di-rects a recombinant chimeric toxin to target cells: in-ternalization is toxin mediated. FASEB J. (1997) 11:1169–1176.
  • SWEENEY EB, FOSS FM, MURPHY JR, VANDERSPEK JC: In-terleukin 7 (11-7) receptor-specific cell killing by DAB (389)11-7: A novel agent for the elimination of IL-7 receptor positive cells. Bioconjugate Chemistry (1998) 9:201–207.
  • KLIMKA A, BARTH S, DRILLICH S et al: A deletion mutant of Pseudomonas exotoxin A fused to recombinant hu-man interleukin-9 (rhIL-9-ETA') shows specific cyto-toxicity against 11-9-expressing cell lines. Cytokines Mol Ther. (1996) 2:139–146.
  • JAIN RK: Delivery of novel therapeutic agents in tu-mors: physiological barriers and strategies. J. Nail Cancer Inst. (1989) 81:570–576.
  • REAL FX, RETTIG WJ, CHESA PG et al: Expression of epi-dermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of dif-ferentiation. Cancer Res. (1986) 46:4726–4731.
  • HENDLER FJ, OZANNE BW: Human squamous cell lung cancers express increased epidermal growth factor re-ceptors. J. Clin. Invest. (1984) 74.647–651.
  • JONES NR, ROSSI ML, GREGORIOU M, HUGHES JT: Inves-tigation of the expression of epidermal growth factor receptor and blood group A antigen in 110 human glio-mas. Neuropathol Appl Neurobiol (1990) 16:185–192.
  • JONES NR, ROSSI ML, GREGORIOU M, HUGHES JT: Epi-dermal growth factor receptor expression in 72 men-ingiomas. Cancer (1990) 66:152–155.
  • REYNOLDS RK, TALAVERA F, ROBERTS JA, HOPKINS MP, MENON KM: Characterization of epidermal growth fac-tor receptor in normal and neoplastic human en-dometrium. Cancer (1990) 66:1967–74.
  • SIEGALL CB, XU Y-H, CHAUDHARY VK et al.: Cytotoxic activities of a fusion protein comprised of TGFa and Pseudomonas exotoxin. FASEB J (1989) 3:2647–2652.
  • BALDWIN RL, KOBRIN MS, TRAN T, PASTAN I, KORC M: Cytotoxic effects of TGF-alpha-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells. Pancreas (1996) 13:16–21.
  • KUNWAR S, PAI LH, PASTAN I: Cytotoxicity and antitu-mor effects of growth factor-toxin fusion proteins on human glioblastoma multiforme cells. J. Neurosurg. (1993) 79:569–576.
  • KAMEYAMA S, KAWAMATA H, PASTAN I, OYASU R: Cyto-toxic effect of a fusion protein from transforming growth factor alpha and Pseudomonas exotoxin on rat and human bladder carcinoma cells in vitro. J. Cancer Res. Clin. Oncol. (1994) 120507–512.
  • EPSTEIN SE, SIEGALL CB, BIRO S et al.: Cytotoxic effects of a recombinant chimeric toxin on rapidly proliferat-ing vascular smooth muscle cells [see comments]. Cir-culation (1991) 84:778–787.
  • DRAOUI M, SIEGALL CB, FITZGERALD D, PASTAN I, MOODY TW: TGF alpha-PE40 inhibits non-small cell lung cancer growth. Life. Sci. (1994) 54:445–453.
  • PHILLIPS PC, LEVOW C, CATTERALL M et al.: Transform-ing growth factor-alpha-Pseudomonas exotoxin fu-sion protein (TGF-alpha-PE38) treatment of subcutaneous and intracranial human glioma and me-dulloblastoma xenografts in athymic mice. Cancer Res. (1994) 54:1008–1015.
  • PAI LH, GALLO MG, FITZGERALD DJ, PASTAN I: Antitu-mor activity of a transforming growth factor a-Pseu-domonas exotoxin fusion protein (TGF-a-PE40). Cancer Res. (1991) 51:2808–2812.
  • HEIMBROOK DC, STIRDIVANT SM, AHERN JD, BALISHIN NL, PATRICK DR et al: Transforming growth factor alpha-Pseudomonas exotoxin fusion protein pro-longs survival of nude mice bearing tumor xenografts. Proc. Natl. Acad. Sci. USA (1990) 87:4697–4701.
  • EDWARDS GM, DEFEO-JONES D, TAI JY et al: Epidermal growth factor receptor binding is affected by struc-tural determinants in the toxin domain of transform-ing growth factor-alpha-Pseudomonas exotoxin fusion proteins. Mol. Cell. Biol. (1989) 9:2860–2867.
  • GOLDBERG MR, HEIMBROOK DC, RUSSO P et al: Phase I clinical study of recombinant oncotoxin TP40 in su-perficial bladder cancer. Clin. Cancer Res. (1995) 1:57–61.
  • SHAW JP, AKIYOSHI DE, ARRIGO DA et al.: Cytotoxic properties of DAB486EGF and DAB389EGF, epidermal growth factor (EGF) receptor-targeted fusion toxins. J. Biol. Chem. (1991) 266:21118–21124.
  • LORIMER IA, KEPPLER-HAFKEMEYER A, BEERS RA et al. Recombinant immunotoxins specific for a mutant epi-dermal growth factor receptor: targeting with a single chain antibody variable domain isolated by phage dis-play. Proc. Natl. Acad. Sci. USA (1996) 93:14815–14820.
  • LORIMER IAJ, WIKSTRAND CJ, BATRA SK, BIGNER DD, PASTAN I: Immunotoxins that target an oncogenic mu-tant epidermal growth factor receptor expressed in human tumors. Clin. Cancer Res. (1995) 1:859–864.
  • BATRA JK, KASPRZYK PG, BIRD RE, PASTAN I, KING CR: Recombinant anti-erbB2 immunotoxins containing Pseudomonasexotoxin. Proc. Natl. Acad. Sci. USA (1992) 89:5867–5871.
  • REITER Y, BRINKMANN U, JUNG S, LEE B, KASPRZYK PG et al.: Improved binding and antitumor activity of a re-combinant anti-erbB2 immunotoxin by disulfide sta-bilization of the Fv fragment. J. Biol. Chem. (1994) 269:18327–18331.
  • WELS W, MORITZ D, SCHMIDT M et al.: Biotechnological and gene therapeutic strategies in cancer treatment. Gene (1995) 159:73–80.
  • JESCHKE M, WELS W, DENGLER W eta].: Targeted inhibi-tion of tumor-cell growth by recombinant heregulin-toxin fusion proteins. Int. J. Cancer (1995) 60:730–739.
  • GRONER B, WICK B, JESCHKE M et al.: Intra-tumoral ap-plication of a heregulin-exotoxin-a fusion protein causes rapid tumor regression without adverse sys-temic or local effects. Int. J. Cancer (1997) 70.682–687.
  • MIXAN B, COHEN BD, BACUS SS, FELL HP, SIEGALL CB: Betacellulin-Pseudomonas toxin fusion proteins bind but are not cytotoxic to cells expressing HER4; correla-tion of EGFR for cytotoxic activity. Oncogene (1998) 16:1209–1215.
  • BENVENISTE R, DANOFF TM, ILEKIS J, CRAIG HR: Epider-mal growth factor receptor numbers in male and fe-male mouse primary hepatocyte cultures. Cell Biochem Funct (1988) 6:231–235.
  • SCHMIDT M, WELS W: Targeted inhibition of tumour cell growth by a bispecific single-chain toxin contain-ing an antibody domain and TGF alpha. Br. J. Cancer (1996) 74:853–862.
  • SCHMIDT M, HYNES NE, GRONER B, WELS W: A bivalent single-chain antibody-toxin specific for ErbB-2 and the EGF receptor. Int. J. Cancer (1996) 65:538–546.
  • PASTAN I, LOVELACE ET, GALLO MG et al.: Characteriza-tion of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. Cancer Res. (1991) 51:3781–3787.
  • PAI LH, BATRA JK, FITZGERALD DJ, WILLINGHAM MC, PASTAN I: Antitumor effects of B3-PE and B3-LysPE40 in a nude mouse model of human breast cancer and the evaluation of B3-PE toxicity in monkeys. Cancer Res. (1992) 52:3189–3193.
  • PASTAN IH, ARCHER GE, MCLENDON RE et al.: Intrathe-cal administration of single-chain immunotoxin, LMB-7 [B3 (FO-PE38], produces cures of carcinomatous meningitis in a rat model. Proc. Natl. Acad. Sci. USA (1995) 92:2765–2769.
  • PAI LH, BATRA JK, FITZGERALD DJ, WILLINGHAM MC, PASTAN I: Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseu-domonas exotoxin [published erratum appears in Proc Natl Acad Sci US A 1991 Jun 1;88(11):5066]. Proc. Natl. Acad. Sci. USA (1991) 88:3358–3362.
  • PAI LH, WITTES R, SETSER A, WILLINGHAM MC, PASTAN I: Treatment of advanced solid tumors with immuno-toxin LMB-1: an antibody linked to Pseudomonas exo-toxin. Nat. Med. (1996) 2.350–353.
  • BRINKMANN U, PAI LH, FITZGERALD DJ, WILLINGHAM M, PASTAN I: B3(Fv) -PE38KDEL, a single-chain immu-notoxin that causes complete regression of a human carcinoma in mice. Proc. Natl. Acad. Sci. USA (1991) 88:8616–8620.
  • SIEGALL CB, GAWLAK SL, CHIN JJ et al.: Cytotoxicity of chimeric (human-murine) monoclonal antibody BR96 IgG, F(ab)2, and Fab' conjugated to Pseudomonas exo-toxin. Bioconjugate Chemistry (1992) 3:302–307.
  • FRIEDMAN PN, MCANDREW SJ, GAWLAK SL et al.: BR96 sFv-PE40, a potent single-chain immunotoxin that se-lectively kills carcinoma cells. Cancer Res. (1993) 53:334–339.
  • SIEGALL CB, CHACE D, MIXAN B et al.: In vitro and in vivo characterization of BR96 sFv-PE40. A single-chain immunotoxin fusion protein that cures human breast carcinoma xenografts in athymic mice and rats. J. Im-munol. (1994) 152:2377–2384.
  • FRIEDMAN PN, CHACE DF, TRAIL PA, SIEGALL CB: Antitu-mor activity of the single-chain immunotoxin BR96 sFv-PE40 against established breast and lung tumor xe-nografts. j Immunol. (1993) 150:3054–3061.
  • SIEGALL CB, LIGGITT D, CHACE D, TEPPER MA, FELL HP: Prevention of immunotoxin-mediated vascular leak syndrome in rats with retention of antitumor activity. Proc. Natl. Acad. Sci. USA (1994) 91:9514–9518.
  • SIEGALL CB, EPSTEIN S, SPEIR E et al: Cytotoxic activity of chimeric proteins composed of acidic fibroblast growth factor and Pseudomonas exotoxin on a variety of cell types. FASEB J (1991) 5:2843–2849.
  • SIEGALL CB, GAWLAK SL, CHACE DF, MERWIN JR, PAS-TAN I: In vivo activities of acidic fibroblast growth fac-t o r-Ps eu domona s exotoxin fusion proteins. Bioconjugate Chemistry (1994) 5:77–83.
  • BIRO S, SIEGALL CB, FU YM et al.: In vitro effects of a re-combinant toxin targeted to the fibroblast growth fac-tor receptor on rat vascular smooth muscle and endothelial cells. Circ. Res. (1992) 71:640–645.
  • GAWLAK SL, PASTAN I, SIEGALL CB: Basic fibroblast growth factor-Pseudomonas exotoxin chimeric pro-teins; comparison with acidic fibroblast growth factor-Pseudomonas exotoxin. Bioconjugate Chemistry (1993) 4:483–489.
  • DAVOL P, FRACKELTON ARJr: The mitotoxin, basic fi-broblast growth factor-saporin, effectively targets human prostatic carcinoma in an animal model. J. Urol. (1996) 156:1174–1179.
  • DAVOL P, BEITZ JG, MOHLER M, YING W, COOK J et al: Saporin toxins directed to basic fibroblast growth fac-tor receptors effectively target human ovarian terato-carcinoma in an animal model. Cancer (1995) 76:79–85.
  • BATOZ M, COLL FRESNO PM, PIZETTE S et al.: A diphthe-ria toxin/fibroblast growth factor 6 mitotoxin selec-tively kills fibroblast growth factor receptor-expressing cell lines. Cell. Growth. Differ. (1995) 6:1143–1149.
  • COLLFRESNO PM, BATOZ M, TARQUIN S, BIRNBAUM D, COULIER F: Cytotoxic activity of a diphtheria toxin/FGF6 mitotoxin on human tumour cell lines. Oncogene (1997) 14:243–247.
  • NEGRO A, SKAPER SD: Production, characterization and cytotoxic properties of a diphtheria toxin-ciliary neurotrophic factor fusion protein. Protein Eng. (1995) 8:175–183.
  • NEGRO A, SKAPER SD: Synthesis, cytotoxic properties and effects on early and late gene induction of a chi-meric diphtheria toxin-leukaemia-inhibitory factor protein. Eur. j Biochem. (1996) 241:507–515.
  • VANDERSPEK JC, SUTHERLAND JA, ZENG H et al.: Inhibi-tion of protein synthesis in small cell lung cancer cells induced by the diphtheria toxin-related fusion protein DAB389 GRP. Cancer Res. (1997) 57:290–294.
  • DEBINSKI W, MINER R, LELAND P, OBIRI NI, PURI RK: Re-ceptor for interleukin (IL) 13 does not interact with114 but receptor for 114 interacts with 1113 on human glioma cells. J. Biol. Chem. (1996) 271:22428–22433.
  • PURI RK, LELAND P, OBIRI NI et al.: Targeting of Interleukin-13 receptor on human renal cell carci-noma cells by a recombinant chimeric protein com-posed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQID. Blood (1996) 87:4333–4339.
  • DEBINSKI W, OBIRI NI, PASTAN I, PURI RK A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J. Biol. Chem. (1995) 270:16775–16780.
  • MAINI A, HILLMAN G, HAAS GP et al.: Interleukin-13 re-ceptors on human prostate carcinoma cell lines repre-sent a novel target for a chimeric protein composed of 11-13 and a mutated form of Pseudomonas exotoxin. J. Urol. (1997) 158:948–953.
  • HUSAIN SR, OBIRI NI, GILL P et al.: Receptor for inter-leukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoin-based chimeric toxin protein. Clin. Cancer Res. (1997) 3:151–156.
  • RAMAKRISHNAN S, OLSON TA, BAUTCH VL, MOHANRAJ D: Vascular endothelial growth factor-toxin conjugate specifically inhibits KDR/flk-l-positive endothelial cell proliferation in vitro and angiogenesis in vivo. Cancer Res. (1996) 56:1324–1330.
  • REITER Y, WRIGHT AF, TONGE DW, PASTAN I: Recombi-nant single-chain and disulfide-stabilized Fv-immunotoxins that cause complete regression of a hu-man colon cancer xenograft in nude mice. Int. J. Cancer (1996) 67:113–123.
  • CHANG K, PASTAN I: Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc. Natl. Acad. Sci. USA (1996) 93:136–140.
  • CHOWDHURY PS, CHANG K, PASTAN I: Isolation of anti-mesothelin antibodies from a phage display li-brary. Mol. Immunol. (1997) 34:9–20.
  • CHOWDHURY PS, VINER JL, BEERS R, PASTAN I: Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage dis-play and construction of a recombinant immunotoxin with anti-tumor activity. Proc. Natl. Acad. Sci. USA (1998) 95:669–674.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.