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Review

Antibody–Enzyme Fusion Proteins for Cancer Therapy

, &
Pages 193-211 | Published online: 15 Feb 2011

Bibliography

  • Bagshawe KD : Antibody directed enzymes revive anti-cancer prodrugs concept.Br. J. Cancer56(5) , 531–532 (1987).
  • Bagshawe KD , SpringerCJ, SearleF et al.: A cytotoxic agent can be generated selectively at cancer sites.Br. J. Cancer58(6) , 700–703 (1988).
  • Senter PD , SaulnierMG, SchreiberGJ et al.: Antitumor effects of antibody–alkaline phosphatase conjugates in combination with etoposide phosphate.Proc. Natl Acad. Sci. USA85(13) , 4842–4846 (1988).
  • Bagshawe KD : Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.Expert Rev. Anticancer Ther.6(10) , 1421–1431 (2006).
  • Bagshawe KD : Targeting: the ADEPT story so far.Curr. Drug Targets10(2) , 152–157 (2009).
  • Senter PD , SpringerCJ: Selective activation of anticancer prodrugs by monoclonal antibody–enzyme conjugates.Adv. Drug Deliv. Rev.53(3) , 247–264 (2001).
  • Wallace PM , MacMasterJF, SmithVF, KerrDE, SenterPD, CosandWL: Intratumoral generation of 5-fluorouracil mediated by an antibody-cytosine deaminase conjugate in combination with 5-fluorocytosine.Cancer Res.54(10) , 2719–2723 (1994).
  • Deckert PM , RennerC, CohenLS et al.: A33scFv-cytosine deaminase: a recombinant protein construct for antibody-directed enzyme–prodrug therapy.Br. J. Cancer88(6) , 937–939 (2003).
  • Kievit E , BershadE, NgE et al.: Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts.Cancer Res.59(7) , 1417–1421 (1999).
  • Coelho V , DerneddeJ, PetrauschU et al.: Design, construction, and in vitro analysis of A33scFv::CDy, a recombinant fusion protein for antibody-directed enzyme prodrug therapy in colon cancer.Int. J. Oncol.31(4) , 951–957 (2007).
  • Panjideh H , Da Silva Coelho V, Dernedde J et al.: Biodistribution and efficacy of 131IA33scFv::CDy, a recombinant antibody–enzyme protein for colon cancer. Int. J. Oncol.32(4) , 925–930 (2008).
  • Goshorn SC , SvenssonHP, KerrDE, SomervilleJE, SenterPD, FellHP: Genetic construction, expression, and characterization of a single chain anti-carcinoma antibody fused to β-lactamase.Cancer Res.53(9) , 2123–2127 (1993).
  • Rodrigues ML , PrestaLG, KottsCE et al.: Development of a humanized disulfide-stabilized anti-p185HER2 Fv-β-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug.Cancer Res.55(1) , 63–70 (1995).
  • Siemers NO , KerrDE, YarnoldS et al.: Construction, expression, and activities of L49-sFv-β-lactamase, a single-chain antibody fusion protein for anticancer prodrug activation.Bioconjug. Chem.8(4) , 510–519 (1997).
  • Kerr DE , VrudhulaVM, SvenssonHP, SiemersNO, SenterPD: Comparison of recombinant and synthetically formed monoclonal antibody-β-lactamase conjugates for anticancer prodrug activation.Bioconjug. Chem.10(6) , 1084–1089 (1999).
  • Vrudhula VM , KerrDE, SiemersNO, DubowchikGM, SenterPD: Cephalosporin prodrugs of paclitaxel for immunologically specific activation by L-49-sFv-β-lactamase fusion protein.Bioorg. Med. Chem. Lett.13(3) , 539–542 (2003).
  • Cortez-Retamozo V , BackmannN, SenterPD et al.: Efficient cancer therapy with a nanobody-based conjugate.Cancer Res.64(8) , 2853–2857 (2004).
  • Alderson RF , TokiBE, RobergeM et al.: Characterization of a CC49-based single-chain fragment-β-lactamase fusion protein for antibody-directed enzyme prodrug therapy (ADEPT).Bioconjug. Chem.17(2) , 410–418 (2006).
  • Phelan RM , OstermeierM, TownsendCA: Design and synthesis of a β-lactamase activated 5-fluorouracil prodrug.Bioorg. Med. Chem. Lett.19(4) , 1261–1263 (2009).
  • Shukla GS , KragDN: Developing bifunctional β-lactamase molecules with built-in target-recognizing module for prodrug therapy: identification of Enterobacter cloacae P99 cephalosporinase loops suitable for randomization and phage-display selection.J. Mol. Recog.22(6) , 425–436 (2009).
  • Lindner HA , LuninVV, AlaryA, HeckerR, CyglerM, MenardR: Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family.J. Biol. Chem.278(45) , 44496–44504 (2003).
  • Buchen S , NgampoloD, MeltonRG et al.: Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure.Br. J. Cancer92(3) , 480–487 (2005).
  • Tuffaha HW , OmarSA: Glucarpidase rescue in a patient with high-dose methotrexate-induced nephrotoxicity.J. Oncol. Pharm.Pract. DOI: 10.1177/1078155209348720 (2009) (Epub ahead of print).
  • Springer CJ , PoonGK, SharmaSK, BagshaweKD: Analysis of antibody–enzyme conjugate clearance by investigation of prodrug and active drug in an ADEPT clinical study.Cell Biophys.24–25 , 193–207 (1994).
  • Springer CJ , DowellR, BurkePJ et al.: Optimization of alkylating agent prodrugs derived from phenol and aniline mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme prodrug therapy (ADEPT).J. Med. Chem.38(26) , 5051–5065 (1995).
  • Sharma SK , BagshaweKD, BurkePJ et al.: Galactosylated antibodies and antibody–enzyme conjugates in antibody-directed enzyme prodrug therapy.Cancer73(Suppl. 3) , 1114–1120 (1994).
  • Napier MP , SharmaSK, SpringerCJ et al.: Antibody-directed enzyme prodrug therapy: efficacy and mechanism of action in colorectal carcinoma.Clin. Cancer Res.6(3) , 765–772 (2000).
  • Michael NP , ChesterKA, MeltonRG et al.: In vitro and in vivo characterisation of a recombinant carboxypeptidase G2::anti-CEA scFv fusion protein.Immunotechnology2(1) , 47–57 (1996).
  • Bhatia J , SharmaSK, ChesterKA et al.: Catalytic activity of an in vivo tumor targeted anti-CEA scFv::carboxypeptidase G2 fusion protein.Int. J. Cancer85(4) , 571–577 (2000).
  • Medzihradszky KF , SpencerDI, SharmaSK et al.: Glycoforms obtained by expression in Pichia pastoris improve cancer targeting potential of a recombinant antibody–enzyme fusion protein.Glycobiology14(1) , 27–37 (2004).
  • Sharma SK , PedleyRB, BhatiaJ et al.: Sustained tumor regression of human colorectal cancer xenografts using a multifunctional mannosylated fusion protein in antibody-directed enzyme prodrug therapy.Clin. Cancer Res.11(2) , 814–825 (2005).
  • Kogelberg H , TolnerB, SharmaSK et al.: Clearance mechanism of a mannosylated antibody–enzyme fusion protein used in experimental cancer therapy.Glycobiology17(1) , 36–45 (2007).
  • Tolner B , SmithL, BegentRH, ChesterKA: Production of recombinant protein in Pichia pastoris by fermentation.Nat. Protoc.1(2) , 1006–1021 (2006).
  • Tolner B , SmithL, BegentRH, ChesterKA: Expanded-bed adsorption immobilized-metal affinity chromatography.Nat. Protoc.1(3) , 1213–1222 (2006).
  • Tolner B , SmithL, HillyerT et al.: From laboratory to Phase I/II cancer trials with recombinant biotherapeutics.Eur. J. Cancer43(17) , 2515–2522 (2007).
  • Mayer A , FrancisRJ, SharmaSK et al.: A Phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody–enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug.Clin. Cancer Res.12(21) , 6509–6516 (2006).
  • Ackerman ME , PawlowskiD, WittrupKD: Effect of antigen turnover rate and expression level on antibody penetration into tumor spheroids.Mol. Cancer Ther.7(7) , 2233–2240 (2008).
  • Bhatia J , SharmaSK, ChesterKA et al.: Catalytic activity of an in vivo tumor targeted anti-CEA scFv::carboxypeptidase G2 fusion protein.Int. J. Cancer85(4) , 571–577 (2000).
  • Thurber GM , SchmidtMM, WittrupKD: Factors determining antibody distribution in tumors.Trends Pharmacol. Sci.29(2) , 57–61 (2008).
  • Thurber GM , SchmidtMM, WittrupKD: Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance.Adv. Drug Deliv. Rev.60(12) , 1421–1434 (2008).
  • Bagshawe KD , SharmaSK: Cyclosporine delays host immune response to antibody enzyme conjugate in ADEPT.Transplant. Proc.28(6) , 3156–3158 (1996).
  • Bagshawe KD : Antibody-directed enzyme prodrug therapy for cancer: its theoretical basis and application.Mol. Med. Today1(9) , 424–431 (1995).
  • Jevsevar S , KunsteljM, PorekarVG: PEGylation of therapeutic proteins.Biotechnol. J.5(1) , 113–128 (2010).
  • Nagata S , PastanI: Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics.Adv. Drug Deliv. Rev.61(11) , 977–985 (2009).
  • Chester KA , BakerM, MayerA: Overcoming the immunologic response to foreign enzymes in cancer therapy.Exp. Rev. Clin. Immunol.1(4) , 549–559 (2005).
  • Spencer DI , RobsonL, PurdyD et al.: A strategy for mapping and neutralizing conformational immunogenic sites on protein therapeutics.Proteomics2(3) , 271–279 (2002).
  • Mayer A , SharmaSK, TolnerB et al.: Modifying an immunogenic epitope on a therapeutic protein: a step towards an improved system for antibody-directed enzyme prodrug therapy (ADEPT).Br. J. Cancer90(12) , 2402–2410 (2004).
  • Weber CA , MehtaPJ, ArditoM, MoiseL, MartinB, De Groot AS: T cell epitope: friend or foe? Immunogenicity of biologics in context. Adv. Drug Deliv. Rev.61(11) , 965–976 (2009).
  • De Groot AS , KnoppPM, MartinW: Deimmunization of therapeutic proteins by T-cell epitope modification.Dev. Biol. (Basel)122 , 171–194 (2005).
  • De Groot AS : Immunomics: discovering new targets for vaccines and therapeutics.Drug Discov. Today11(5–6) , 203–209 (2006).
  • De Groot AS , MartinW: Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics.Clin. Immunol.131(2) , 189–201 (2009).
  • Harding FA , LiuAD, SticklerM et al.: A β-lactamase with reduced immunogenicity for the targeted delivery of chemotherapeutics using antibody-directed enzyme prodrug therapy.Mol. Cancer Ther.4(11) , 1791–1800 (2005).
  • Bosslet K , CzechJ, HoffmannD: Tumor-selective prodrug activation by fusion protein-mediated catalysis.Cancer Res.54(8) , 2151–2159 (1994).
  • Haisma HJ , SerneeMF, HooijbergE et al.: Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human β-glucuronidase for antibody-directed enzyme prodrug therapy.Blood92(1) , 184–190 (1998).
  • De Graaf M , BovenE, OosterhoffD et al.: A fully human anti-Ep-CAM scFv-β-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug.Br. J. Cancer86(5) , 811–818 (2002).
  • Biela BH , KhawliLA, HuP, EpsteinAL: Chimeric TNT-3/human β-glucuronidase fusion proteins for antibody-directed enzyme prodrug therapy (ADEPT).Cancer Biother. Radiopharm.18(3) , 339–353 (2003).
  • Hao XK , LiuJY, YueQH, WuGJ, BaiYJ, YinY: In vitro and in vivo prodrug therapy of prostate cancer using anti-γ-Sm-scFv/hCPA fusion protein.Prostate66(8) , 858–866 (2006).
  • Afshar S , AsaiT, MorrisonSL: Humanized ADEPT comprised of an engineered human purine nucleoside phosphorylase and a tumor targeting peptide for treatment of cancer.Mol. Cancer Ther.8(1) , 185–193 (2009).
  • Lowe H , TolnerB, KogelbergH et al.: A novel mutated human enzyme with a bis-chloro-phenol prodrug for antibody directed enzyme prodrug therapy (ADEPT). Presented at: The National Cancer Research Institute (NCRI) Cancer Conference 2007. Birmingham, UK, 30 September–3 October 2007.
  • Graff CP , ChesterK, BegentR, WittrupKD: Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37°C.Protein Eng. Des. Sel.17(4) , 293–304 (2004).
  • Pollack SJ , JacobsJW, SchultzPG: Selective chemical catalysis by an antibody.Science234(4783) , 1570–1573 (1986).
  • Tramontano A , JandaKD, LernerRA: Catalytic antibodies.Science234(4783) , 1566–1570 (1986).
  • Nevinsky GA , BunevaVN: Peculiarities of abzymes from sera and milk of healthy donors and patients with autoimmune and viral diseases.Biochemistry74(9) , 945–961 (2009).
  • Xu Y , YamamotoN, JandaKD: Catalytic antibodies: hapten design strategies and screening methods.Bioorg. Med. Chem.12(20) , 5247–5268 (2004).
  • Ikhmyangan EN , VasilenkoNL, BunevaVN, NevinskyGA: IgG antibodies with peroxidase-like activity from the sera of healthy Wistar rats.FEBS Lett.579(18) , 3960–3964 (2005).
  • Belogurov AJ , KozyrA, PonomarenkoN, GabibovA: Catalytic antibodies: balancing between Dr. Jekyll and Mr. Hyde.Bioessays31(11) , 1161–1171 (2009).
  • Abraham S , GuoF, LiLS et al.: Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation.Proc. Natl Acad. Sci. USA104(13) , 5584–5589 (2007).
  • Shabat D , LodeHN, PertlU et al.: In vivo activity in a catalytic antibody-prodrug system: antibody catalyzed etoposide prodrug activation for selective chemotherapy.Proc. Natl Acad. Sci. USA98(13) , 7528–7533 (2001).
  • Wojcik T , Kiec-KononowiczK: Catalytic activity of certain antibodies as a potential tool for drug synthesis and for directed prodrug therapies.Curr. Med. Chem.15 , 1606–1615 (2008).
  • Huo R , WeiJ, XuJ et al.: Human catalytic antibody Se-scFv-B3 with high glutathione peroxidase activity.J. Mol. Recognit.21(5) , 324–329 (2008).
  • Xu J , SongJ, YanF et al.: Improving GPX activity of selenium-containing human single-chain Fv antibody by site-directed mutation based on the structural analysis.J. Mol. Recognit.22(4) , 293–300 (2009).
  • Nieva J , Wentworth Jr P: The antibody-catalyzed water oxidation pathway – a new chemical arm to immune defense? Trends Biochem. Sci.29(5) , 274–278 (2004).
  • Smith BM : Catalytic methods for the destruction of chemical warfare agents under ambient conditions.Chem. Soc. Rev.37(3) , 470–478 (2008).
  • Xu Y , HixonMS, YamamotoN et al.: Antibody-catalyzed anaerobic destruction of methamphetamine.Proc. Natl Acad. Sci. USA104(10) , 3681–3686 (2007).
  • McKenzie KM , MeeJM, RogersCJ, HixonMS, KaufmannGF, JandaKD: Identification and characterization of single chain anti-cocaine catalytic antibodies.J. Mol. Biol.365(3) , 722–731 (2007).
  • Robertson MP , ScottWG: Biochemistry: designer enzymes.Nature448(7155) , 757–758 (2007).
  • Sapparapu G , PlanqueSA, NishiyamaY, FoungSK, PaulS: Antigen-specific proteolysis by hybrid antibodies containing promiscuous proteolytic light chains paired with an antigen-binding heavy chain.J. Biol. Chem.284(36) , 24622–24633 (2009).
  • Phichith D , BunS, Padiolleau-LefevreS et al.: Mutational and inhibitory analysis of a catalytic antibody. Implication for drug discovery.Mol. Immunol.47(2–3) , 348–356 (2009).
  • Blakey DC , BurkePJ, DaviesDH et al.: ZD2767, an improved system for antibody-directed enzyme prodrug therapy that results in tumor regressions in colorectal tumor xenografts.Cancer Res.56(14) , 3287–3292 (1996).
  • Monks NR , BlakeyDC, CurtinNJ, EastSJ, HeuzeA, NewellDR: Induction of apoptosis by the ADEPT agent ZD2767: comparison with the classical nitrogen mustard chlorambucil and a monofunctional ZD2767 analogue.Br. J. Cancer85(5) , 764–771 (2001).
  • McHugh PJ , SpanswickVJ, HartleyJA: Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance.Lancet Oncol.2(8) , 483–490 (2001).
  • Tietze LF , KrewerB: Antibody-directed enzyme prodrug therapy: a promising approach for a selective treatment of cancer based on prodrugs and monoclonal antibodies.Chem. Bio. Drug Des.74(3) , 205–211 (2009).
  • Rooseboom M , CommandeurJN, VermeulenNP: Enzyme-catalyzed activation of anticancer prodrugs.Pharmacol. Rev.56(1) , 53–102 (2004).
  • Rautio J , KumpulainenH, HeimbachT et al.: Prodrugs: design and clinical applications.Nat. Rev. Drug Discov.7(3) , 255–270 (2008).
  • Kim WC , LeeCH: The role of mammalian ribonucleases (RNases) in cancer.Biochim. Biophys. Acta1796(2) , 99–113 (2009).
  • Boix E , NoguesMV: Mammalian antimicrobial proteins and peptides: overview on the RNase A superfamily members involved in innate host defence.Mol. Biosyst.3(5) , 317–335 (2007).
  • Schein CH : From housekeeper to microsurgeon: the diagnostic and therapeutic potential of ribonucleases.Nat. Biotech.15(6) , 529–536 (1997).
  • D‘Alessio G , Di Donato A, Mazzarella L, Piccoli R: Seminal RNases: importance of diversity. In: Ribonucleases: Structures and Functions. D‘Alessio G, Riordan JF (Eds). Academic Press Inc., MA, USA, 383–423 (1997).
  • Saxena SK , RybakSM, WinklerG et al.: Comparison of RNases and toxins upon injection into Xenopus oocytes.J. Biol. Chem.266(31) , 21208–21214 (1991).
  • Rybak SM , SaxenaSK, AckermanEJ, YouleRJ: Cytotoxic potential of ribonuclease and ribonuclease hybrid proteins.J. Biol. Chem.266(31) , 21202–21207 (1991).
  • Ilinskaya ON , KoschinskiA, MitkevichVA et al.: Cytotoxicity of RNases is increased by cationization and counteracted by K(Ca) channels.Biochem. Biophys. Res. Commun.314(2) , 550–554 (2004).
  • Johnson RJ , McCoyJG, BingmanCA, Phillips Jr GN, Raines RT: Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. J. Mol. Bio.368(2) , 434–449 (2007).
  • Futami J , YamadaH: Design of cytotoxic ribonucleases by cationization to enhance intracellular protein delivery.Curr. Pharm. Biotechnol.9(3) , 180–184 (2008).
  • Fuchs SM , RutkoskiTJ, KungVM, GroeschlRT, RainesRT: Increasing the potency of a cytotoxin with an arginine graft.Protein Eng. Des. Sel.20(10) , 505–509 (2007).
  • Ilinskaya ON , KoschinskiA, ReppH et al.: RNase-induced apoptosis:Fate of calcium-activated potassium channels.Biochimie90(5) , 717–725 (2008).
  • Zhao H , ArdeltB, ArdeltW, ShogenK, DarzynkiewiczZ: The cytotoxic ribonuclease onconase targets RNA interference (siRNA).Cell Cycle7(20) , 3258–3261 (2008).
  • Iordanov MS , RyabininaOP, WongJ et al.: Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis.Cancer Res.60(7) , 1983–1994 (2000).
  • Spalletti-Cernia D , SorrentinoR, DiGS et al.: Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase-mediated induction of apoptosis.J. Clin. Endocrinol. Metab.88(6) , 2900–2907 (2003).
  • Sorrentino S , NaddeoM, RussoA, D‘AlessioG: Degradation of double-stranded RNA by human pancreatic ribonuclease: crucial role of noncatalytic basic amino acid residues.Biochemistry42(34) , 10182–10190 (2003).
  • Blaszczyk J , GanJ, TropeaJE, CourtDL, WaughDS, JiX: Noncatalytic assembly of ribonuclease III with double-stranded RNA.Structure12(3) , 457–466 (2004).
  • Alford S , PearsonJ, CaretteA, InghamR, HowardP: α-sarcin catalytic activity is not required for cytotoxicity.BMC Biochem.10(1) , 9 (2009).
  • Pastan I , HassanR, FitzGeraldDJ, KreitmanRJ: Immunotoxin treatment of cancer.Annu. Rev. Med.58(1) , 221–237 (2007).
  • Kreitman RJ : Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies.BioDrugs23(1) , 1–13 (2009).
  • Potala S , SahooSK, VermaRS: Targeted therapy of cancer using diphtheria toxin-derived immunotoxins.Drug Discov. Today13(17–18) , 807–815 (2008).
  • Foss F : Clinical experience with denileukin diftitox (ONTAK).Semin. Oncol.33(Suppl. 3) , 11–16 (2006).
  • Stirpe F , BattelliMG: Ribosome-inactivating proteins: progress and problems.Cell Mol. Life Sci.63(16) , 1850–1866 (2006).
  • Cao Y , MarksJD, MarksJW, CheungLH, KimS, RosenblumMG: Construction and characterization of novel, recombinant immunotoxins targeting the Her2/neu oncogene product: in vitro and in vivo studies.Cancer Res.69(23) , 8987–8995 (2009).
  • Rosenberg HF : RNase A ribonucleases and host defense: an evolving story.J. Leukoc. Biol.83(5) , 1079–1087 (2008).
  • Dickson KA , HaigisMC, RainesRT: Ribonuclease inhibitor: structure and function. In: Progress in Nucleic Acid Research and Molecular Biology. Kivie M (Ed.). Academic Press Inc., MA, USA, 349–374 (2005)
  • Rutkoski TJ , RainesRT: Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.Curr. Pharm. Biotechnol.9(3) , 185–189 (2008).
  • De Lorenzo C , Di Malta C, Cali G, Troise F, Nitsch L, D‘Alessio G: Intracellular route and mechanism of action of ERB-hRNase, a human anti-ErbB2 anticancer immunoagent. FEBS Lett.581(2) , 296–300 (2007).
  • Peracaula R , ClearyKR, LorenzoJ, de Llorens R, Frazier ML: Human pancreatic ribonuclease 1: expression and distribution in pancreatic adenocarcinoma. Cancer89(6) , 1252–1258 (2000).
  • Fernandez-Salas E , PeracaulaR, FrazierML, de Llorens R: Ribonucleases expressed by human pancreatic adenocarcinoma cell lines. Eur. J. Biochem.267(5) , 1484–1494 (2000).
  • Rybak SM , NewtonDL: Natural and engineered cytotoxic ribonucleases: therapeutic potential.Exp. Cell Res.253(2) , 325–335 (1999).
  • Zewe M , RybakSM, DubelS et al.: Cloning and cytotoxicity of a human pancreatic RNase immunofusion.Immunotechnology3(2) , 127–136 (1997).
  • Erickson HA , JundMD, PennellCA: Cytotoxicity of human RNase-based immunotoxins requires cytosolic access and resistance to ribonuclease inhibition.Protein Eng. Des. Sel.19(1) , 37–45 (2006).
  • De Lorenzo C , NigroA, PiccoliR, D‘AlessioG: A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells.FEBS Lett.516(1–3) , 208–212 (2002).
  • De Lorenzo C , ArcielloA, CozzolinoR et al.: A fully human antitumor immunoRNase selective for ErbB-2-positive carcinomas.Cancer Res.64(14) , 4870–4874 (2004).
  • Leich F , StohrN, RietzA, Ulbrich-HofmannR, ArnoldU: Endocytotic internalization as a crucial factor for the cytotoxicity of ribonucleases.J. Biol. Chem.282(38) , 27640–27646 (2007).
  • Riccio G , BorrielloM, D‘AlessioG, De Lorenzo C: A novel human antitumor dimeric immunoRNase. J. Immunother.31(5) (2008).
  • De Lorenzo C , D‘AlessioG: Human anti-ErbB2 immunoagents – immunoRNases and compact antibodies.FEBS J.276(6) , 1527–1535 (2009).
  • Braschoss S , HirschB, DubelS, SteinH, DurkopH: New anti-CD30 human pancreatic ribonuclease-based immunotoxin reveals strong and specific cytotoxicity in vivo.Leuk. Lymphoma48(6) , 1179–1186 (2007).
  • Menzel C , SchirrmannT, KonthurZ, JostockT, DubelS: Human antibody RNase fusion protein targeting CD30+ lymphomas.Blood111(7) , 3830–3837 (2008).
  • Dickson KA , RainesRT: Silencing an inhibitor unleashes a cytotoxic enzyme.Biochemistry48(23) , 5051–5053 (2009).
  • Bosch M , BenitoA, RiboM, PuigT, BeaumelleB, VilanovaM: A nuclear localization sequence endows human pancreatic ribonuclease with cytotoxic activity.Biochemistry43(8) , 2167–2177 (2004).
  • Leland PA , StaniszewskiKE, KimBM, RainesRT: Endowing human pancreatic ribonuclease with toxicity for cancer cells.J. Biol. Chem.276(46) , 43095–43102 (2001).
  • Merlino A , AvellaG, DiGS et al.: Structural features for the mechanism of antitumor action of a dimeric human pancreatic ribonuclease variant.Protein Sci.18(1) , 50–57 (2009).
  • Vihinen P , KallioinenM, VuoristoMS et al.: Serum angiogenin levels predict treatment response in patients with stage IV melanoma.Clin. Exp. Metastasis24(7) , 567–574 (2007).
  • Tello-Montoliu A , PatelJV, LipGY: Angiogenin: a review of the pathophysiology and potential clinical applications.J. Thromb. Haemost.4(9) , 1864–1874 (2006).
  • Newton DL , XueY, OlsonKA, FettJW, RybakSM: Angiogenin single-chain immunofusions: influence of peptide linkers and spacers between fusion protein domains.Biochemistry35(2) , 545–553 (1996).
  • Russo N , NobileV, Di Donato A, Riordan JF, Vallee BL: The C-terminal region of human angiogenin has a dual role in enzymatic activity. Proc. Natl Acad. Sci. USA93(8) , 3243–3247 (1996).
  • Krauss J , ArndtMA, VuBK, NewtonDL, RybakSM: Targeting malignant B-cell lymphoma with a humanized anti-CD22 scFv-angiogenin immunoenzyme.Br. J. Haematol.128(5) , 602–609 (2005).
  • Arndt MA , KraussJ, SchwarzenbacherR, VuBK, GreeneS, RybakSM: Generation of a highly stable, internalizing anti-CD22 single-chain Fv fragment for targeting non-Hodgkin‘s lymphoma.Int. J. Cancer107(5) , 822–829 (2003).
  • Arndt MAE , KraussJ, RybakSM: Antigen binding and stability properties of non-covalently linked anti-CD22 single-chain Fv dimers.FEBS Lett.578(3) , 257–261 (2004).
  • Arndt MA , KraussJ, VuBK, NewtonDL, RybakSM: A dimeric angiogenin immunofusion protein mediates selective toxicity toward CD22+ tumor cells.J. Immunother.28(3) , 245–251 (2005).
  • Huhn M , SasseS, TurMK et al.: Human angiogenin fused to human CD30 ligand (Ang-CD30L) exhibits specific cytotoxicity against CD30-positive lymphoma.Cancer Res.61(24) , 8737–8742 (2001).
  • Barth S , MattheyB, HuhnM, DiehlV, EngertA: CD30L-ETA: a new recombinant immunotoxin based on the CD30 ligand for possible use against human lymphoma.Cytokines Cell Mol. Ther.5(2) , 69–78 (1999).
  • Stocker M , TurMK, SasseS, KrussmannA, BarthS, EngertA: Secretion of functional anti-CD30-angiogenin immunotoxins into the supernatant of transfected 293T-cells.Protein Expr. Purif.28(2) , 211–219 (2003).
  • Rybak SM , HoogenboomHR, MeadeHM, RausJC, SchwartzD, YouleRJ: Humanization of immunotoxins.Proc. Natl Acad. Sci. USA89(8) , 3165–3169 (1992).
  • Newton DL , PollockD, DiTullioP et al.: Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice.J. Immunol. Methods231(1–2) , 159–167 (1999).
  • Lee JE , RainesRT: Cytotoxicity of bovine seminal ribonuclease: monomer versus dimer.Biochemistry44(48) , 15760–15767 (2005).
  • Leland PA , RainesRT: Cancer chemotherapy–ribonucleases to the rescue.Chem. Biol.8(5) , 405–413 (2001).
  • Ardelt W , ArdeltB, DarzynkiewiczZ: Ribonucleases as potential modalities in anticancer therapy.Eur. J. Pharmacol.625(1–3) , 181–189 (2009).
  • Makarov AA , KolchinskyA, IlinskayaON: Binase and other microbial RNases as potential anticancer agents.Bioessays30(8) , 781–790 (2008).
  • Hartley RW : Homology between prokaryotic and eukaryotic ribonucleases.J. Mol. Evol.15(4) , 355–358 (1980).
  • Hill C , DodsonG, HeinemannU et al.: The structural and sequence homology of a family of microbial ribonucleases.Trends Biochem. Sci.8(10) , 364–369 (1983).
  • Lacadena J , varez-GarciaE, Carreras-SangraN et al.: Fungal ribotoxins: molecular dissection of a family of natural killers.FEMS Microbiol. Rev.31(2) , 212–237 (2007).
  • Buckle AM , SchreiberG, FershtAR: Protein–protein recognition: crystal structural analysis of a barnase-barstar complex at 2.0-A resolution.Biochemistry33(30) , 8878–8889 (1994).
  • Prior TI , FitzGeraldDJ, PastanI: Translocation mediated by domain II of Pseudomonas exotoxin A: transport of barnase into the cytosol.Biochemistry31(14) , 3555–3559 (1992).
  • Prior TI , KunwarS, PastanI: Studies on the activity of barnase toxins in vitro and in vivo.Bioconjug. Chem.7(1) , 23–29 (1996).
  • Edelweiss E , BalandinTG, IvanovaJL et al.: Barnase as a new therapeutic agent triggering apoptosis in human cancer cells.PLoS One3(6) , E2434 (2008).
  • Balandin T , EdelweissE, AndronovaN, TreshalinaE, SapozhnikovA, DeyevS: Antitumor activity and toxicity of anti-HER2 immunoRNase scFv 4D5-dibarnase in mice bearing human breast cancer xenografts.Invest. New Drugs (2009).
  • Darzynkiewicz Z , CarterSP, MikulskiSM, ArdeltWJ, ShogenK: Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent.Cell Tissue Kinet.21(3) , 169–182 (1988).
  • Smith MR , NewtonDL, MikulskiSM, RybakSM: Cell cycle-related differences in susceptibility of NIH/3T3 cells to ribonucleases.Exp. Cell Res.247(1) , 220–232 (1999).
  • Saxena SK , SirdeshmukhR, ArdeltW, MikulskiSM, ShogenK, YouleRJ: Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family.J. Biol. Chem.277(17) , 15142–15146 (2002).
  • Costanzi J , SidranskyD, NavonA, GoldsweigH: Ribonucleases as a novel proapoptotic anticancer strategy: review of the preclinical and clinical data for ranpirnase.Cancer Inves.23(7) , 643–650 (2005).
  • Lee I : Ranpirnase (onconase), a cytotoxic amphibian ribonuclease, manipulates tumor physiological parameters as a selective killer and a potential enhancer for chemotherapy and radiation in cancer therapy.Expert Opin. Biol. Ther.8(6) , 813–827 (2008).
  • Mikulski SM , CostanziJJ, VogelzangNJ et al.: Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma.J. Clin. Oncol.20(1) , 274–281 (2002).
  • Newton DL , HansenHJ, LiuH et al.: Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents.Crit. Rev. Oncol. Hematol.39(1–2) , 79–86 (2001).
  • Hursey M , NewtonDL, HansenHJ, RubyD, GoldenbergDM, RybakSM: Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: a new generation of therapeutics.Leuk. Lymphoma43(5) , 953–959 (2002).
  • Chang CH , SapraP, VanamaSS, HansenHJ, HorakID, GoldenbergDM: Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin.Blood106(13) , 4308–4314 (2005).
  • Krauss J , ArndtMAE, ZhuZ et al.: Impact of antibody framework residue VH-71 on the stability of a humanised anti-MUC1 scFv and derived immunoenzyme.Br. J. Cancer90(9) , 1863–1870 (2004).
  • Krauss J , ArndtMAE, VuBK, NewtonDL, SeeberS, RybakSM: Efficient killing of CD22+ tumor cells by a humanized diabody-RNase fusion protein.Biochem. Biophys. Res. Commun.331(2) , 595–602 (2005).
  • Youle RJ , D‘AlessioG. Antitumor Ribonucleases. In: Ribonucleases: Structures and Functions. D‘Alessio G, Riordan JF (Eds). Academic Press Inc., MA, USA, 491–514 (1997)
  • Matousek J , SoucekJ, SlavikT, TomanekM, LeeJE, RainesRT: Comprehensive comparison of the cytotoxic activities of onconase and bovine seminal ribonuclease.Comp. Biochem. Physiol. C Toxicol. Pharmacol.136(4) , 343–356 (2003).
  • Spalletti-Cernia D , SorrentinoR, DiGS et al.: Highly selective toxic and proapoptotic effects of two dimeric ribonucleases on thyroid cancer cells compared to the effects of doxorubicin.Br. J. Cancer90(1) , 270–277 (2004).
  • Sica F , DiFA, MerlinoA, MazzarellaL: Structure and stability of the noncovalent swapped dimer of bovine seminal ribonuclease: an enzyme tailored to evade ribonuclease protein inhibitor.J. Biol. Chem.279(35) , 36753–36760 (2004).
  • Merlino A , ErcoleC, PiconeD, PizzoE, MazzarellaL, SicaF: The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped noncovalent form of the enzyme.J. Mol. Biol.376(2) , 427–437 (2008).
  • Bracale A , Spalletti-CerniaD, MastronicolaM et al.: Essential stations in the intracellular pathway of cytotoxic bovine seminal ribonuclease.Biochem. J.362(Pt 3) , 553–560 (2002).
  • Bracale A , CastaldiF, NitschL, D‘AlessioG: A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action.Eur. J. Biochem.270(9) , 1980–1987 (2003).
  • Benito A , RiboM, VilanovaM: On the track of antitumour ribonucleases.Mol. Biosyst.1(4) , 294–302 (2005).
  • Ercole C , ColamarinoRA, PizzoE, FogolariF, SpadacciniR, PiconeD: Comparison of the structural and functional properties of RNase A and BS-RNase: a stepwise mutagenesis approach.Biopolymers91(12) , 1009–1017 (2009).
  • Deonarain MP , EpenetosAA: Design, characterization and antitumor cytotoxicity of a panel of recombinant, mammalian ribonuclease-based immunotoxins.Br. J. Cancer77(4) , 537–546 (1998).
  • Mathew M , VermaRS: Humanized immunotoxins: a new generation of immunotoxins for targeted cancer therapy.Cancer Sci.100(8) , 1359–1365 (2009).
  • Rosenblum MG , BarthS: Development of novel, highly cytotoxic fusion constructs containing granzyme B: unique mechanisms and functions.Curr. Pharm. Des.15(23) , 2676–2692 (2009).
  • Heusel JW , WesselschmidtRL, ShrestaS, RussellJH, LeyTJ: Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells.Cell76(6) , 977–987 (1994).
  • Thomas DA , DuC, XuM, WangX, LeyTJ: DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis.Immunity12(6) , 621–632 (2000).
  • Talanian RV , YangX, TurbovJ et al.: Granule-mediated killing: pathways for granzyme B-initiated apoptosis.J. Exp. Med.186(8) , 1323–1331 (1997).
  • Heibein JA , GopingIS, BarryM et al.: Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members Bid and Bax.J. Exp. Med.192(10) , 1391–1402 (2000).
  • Trapani JA , JansDA, JansPJ, SmythMJ, BrowneKA, SuttonVR: Efficient nuclear targeting of granzyme B and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent.J. Biol. Chem.273(43) , 27934–27938 (1998).
  • Dalken B , GiesubelU, KnauerSK, WelsWS: Targeted induction of apoptosis by chimeric granzyme B fusion proteins carrying antibody and growth factor domains for cell recognition.Cell Death Differ.13(4) , 576–585 (2005).
  • Zhao J , ZhangLH, JiaLT et al.: Secreted antibody/granzyme B fusion protein stimulates selective killing of HER2-overexpressing tumor cells.J. Biol. Chem.279(20) , 21343–21348 (2004).
  • Stahnke B , ThepenT, StockerM et al.: Granzyme B-H22(scFv), a human immunotoxin targeting CD64 in acute myeloid leukemia of monocytic subtypes.Mol. Cancer Ther.7(9) , 2924–2932 (2008).
  • Liu Y , CheungLH, HittelmanWN, RosenblumMG: Targeted delivery of human proapoptotic enzymes to tumor cells: in vitro studies describing a novel class of recombinant highly cytotoxic agents.Mol. Cancer Ther.2(12) , 1341–1350 (2003).
  • Liu Y , ZhangW, NiuT et al.: Targeted apoptosis activation with GrB/scFvMEL modulates melanoma growth, metastatic spread, chemosensitivity, and radiosensitivity.Neoplasia8(2) , 125–135 (2006).
  • Godal R , KeilholzU, UharekL et al.: Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2.Blood107(8) , 3205–3211 (2006).
  • Xu YM , WangLF, JiaLT et al.: A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2-overexpressing tumors.J. Immunol.173(1) , 61–67 (2004).
  • Wang LF , ZhouY, XuYM et al.: A caspase-6 and anti-HER2 antibody chimeric tumor-targeted proapoptotic molecule decreased metastasis of human osteosarcoma.Cancer Inves.27(7) , 774–780 (2009).
  • Woo EJ , KimYG, KimMS et al.: Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway.Mol. Cell14(4) , 531–539 (2004).
  • Newton DL , NichollsPJ, RybakSM, YouleRJ: Expression and characterization of recombinant human eosinophil-derived neurotoxin and eosinophil-derived neurotoxin-anti-transferrin receptor sFv.J. Biol. Chem.269(43) , 26739–26745 (1994).
  • Newton DL , Rybak SM: Unique recombinant human ribonuclease and inhibition of Kaposi‘s sarcoma cell growth. J. Natl Cancer Inst.90(23) , 1787–1791 (1998).
  • Takashi M , MidoriK, HirokoT et al.: Growth inhibition of mammalian cells by eosinophil cationic protein.Eur. J. Biochem.269(1) , 307–316 (2002).

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