Translating antibody directed enzyme prodrug therapy (ADEPT) and prospects for combination

References

• Aschheim S, Varangot J, Vassy S, et al. [Positive biological pregnancy tests and false pregnancy]. Bull Fed Soc Gynecol Obstet Lang Fr. 1952;4(4):664–667.
   PubMedGoogle Scholar
• Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965 Sep 1;122(3):467–481.
   PubMed Web of Science ®Google Scholar
• Wilde CE, Orr AH, Bagshawe KD. A radioimmunoassay for human chorionic gonadotrophin. Nature. 1965 Jan 9;205:191–192.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD, Wilde CE, Orr AH. Radioimmunoassay for human chorionic gonadotrophin and luteinising hormone. Lancet. 1966 May 21;1(7447):1118–1121.
   PubMed Web of Science ®Google Scholar
• Farrands PA, Perkins AC, Pimm MV, et al. Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet. 1982 Aug 21;2(8295):397–400.
   PubMed Web of Science ®Google Scholar
• Primus FJ, Wang RH, Goldenberg DM, et al. Localization of human GW-39 tumors in hamsters by radiolabeled heterospecific antibody to carcinoembryonic antigen. Cancer Res. 1973 Nov;33(11):2977–2982.
   PubMed Web of Science ®Google Scholar
• Mach JP, Carrel S, Merenda C, et al. In vivo localisation of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice. Nature. 1974 Apr 19;248(5450):704–706.
   PubMed Web of Science ®Google Scholar
• Mach JP, Carrel S, Forni M, et al. Tumor localization of radiolabeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation. N Engl J Med. 1980 Jul 3;303(1):5–10.
   PubMed Web of Science ®Google Scholar
• Goldenberg DM, DeLand F, Kim E, et al. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med. 1978 Jun 22;298(25):1384–1386.
   PubMed Web of Science ®Google Scholar
• Begent RH, Searle F, Stanway G, et al. Radioimmunolocalization of tumours by external scintigraphy after administration of 131I antibody to human chorionic gonadotrophin: preliminary communication. J R Soc Med. 1980 Sep;73(9):624–630.
   PubMed Web of Science ®Google Scholar
• Begent RH, Keep PA, Green AJ, et al. Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody. Lancet. 1982 Oct 2;2(8301):739–742.
   PubMed Web of Science ®Google Scholar
• Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7; 256(5517):495–497.
   PubMed Web of Science ®Google Scholar
• Wold ED, Smider VV, Felding BH. Antibody therapeutics in oncology. Immunotherapy (Los Angel). 2016 Mar;2(1):108.
   PubMedGoogle Scholar
• Pasquetto MV, Vecchia L, Covini D, et al. Targeted drug delivery using immunoconjugates: principles and applications. J Immunother. 2011 Nov–Dec;34(9):611–628. DOI:10.1097/CJI.0b013e318234ecf5
   PubMed Web of Science ®Google Scholar
• Casi G, Neri D. Antibody-drug conjugates and small molecule-drug conjugates: opportunities and challenges for the development of selective anticancer cytotoxic agents. J Med Chem. 2015 Nov 25;58(22):8751–8761.
   PubMed Web of Science ®Google Scholar
• Govindan SV, Sharkey RM, Goldenberg DM. Prospects and progress of antibody-drug conjugates in solid tumor therapies. Expert Opin Biol Ther. 2016 Apr 4;16(7):883–893.
   PubMed Web of Science ®Google Scholar
• Papachristos A, Pippa N, Demetzos C, et al. Antibody-drug conjugates: a mini-review. The synopsis of two approved medicines. Drug Deliv. 2016;23(5):1662–1666.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD. Antibody directed enzymes revive anti-cancer prodrugs concept. Br J Cancer. 1987 Nov;56(5):531–532.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD, Springer CJ, Searle F, et al. A cytotoxic agent can be generated selectively at cancer sites. Br J Cancer. 1988 Dec;58(6):700–703.
   PubMed Web of Science ®Google Scholar
• Senter PD, Saulnier MG, Schreiber GJ, et al. Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. Proc Natl Acad Sci USA. 1988 Jul;85(13):4842–4846.
   PubMed Web of Science ®Google Scholar
• Cheng TL, Wei SL, Chen BM, et al. Bystander killing of tumour cells by antibody-targeted enzymatic activation of a glucuronide prodrug. Br J Cancer. 1999 Mar;79(9–10):1378–1385. DOI:10.1038/sj.bjc.6690221 .
   PubMed Web of Science ®Google Scholar
• Bagshawe KD. Targeting: the ADEPT story so far. Curr Drug Targets. 2009 Feb;10(2):152–157.
   PubMed Web of Science ®Google Scholar
• Schellmann N, Deckert PM, Bachran D, et al. Targeted enzyme prodrug therapies. Mini Rev Med Chem. 2010 Sep;10(10):887–904. DOI:10.2174/138955710792007196 .
   PubMed Web of Science ®Google Scholar
• Weidle UH, Tiefenthaler G, Georges G. Proteases as activators for cytotoxic prodrugs in antitumor therapy. Cancer Genomics Proteomics. 2014;11(2):67–79.
   PubMed Web of Science ®Google Scholar
• Tietze LF, Schmuck K. Prodrugs for targeted tumor therapies: recent developments in ADEPT, GDEPT and PMT. Curr Pharm Des. 2011;17(32):3527–3547.
   PubMed Web of Science ®Google Scholar
• Senter PD, Schreiber GJ, Hirschberg DL, et al. Enhancement of the in vitro and in vivo antitumor activities of phosphorylated mitomycin C and etoposide derivatives by monoclonal antibody-alkaline phosphatase conjugates. Cancer Res. 1989 Nov 1;49(21):5789–5792.
   PubMed Web of Science ®Google Scholar
• Wallace PM, Senter PD. In vitro and in vivo activities of monoclonal antibody-alkaline phosphatase conjugates in combination with phenol mustard phosphate. Bioconjug Chem. 1991 Sep–Oct;2(5):349–352.
   PubMed Web of Science ®Google Scholar
• Mamber SW, Mikkilineni AB, Pack EJ, et al. Tubulin polymerization by paclitaxel (taxol) phosphate prodrugs after metabolic activation with alkaline phosphatase. J Pharmacol Exp Ther. 1995 Aug;274(2):877–883.
   PubMed Web of Science ®Google Scholar
• Abraham R, Aman N, von Borstel R, et al. Conjugates of COL-1 monoclonal antibody and beta-D-galactosidase can specifically kill tumor cells by generation of 5-fluorouridine from the prodrug beta-D-galactosyl-5-fluorouridine. Cell Biophys. 1994;24-25:127–133.
   PubMedGoogle Scholar
• Adidala R, Devalapally H, Srivari C, et al. An improved synthesis of lysosomal activated mustard prodrug for tumor-specific activation and its cytotoxic evaluation. Drug Dev Ind Pharm. 2012 Sep;38(9):1047–1053. DOI:10.3109/03639045.2011.637932
   PubMed Web of Science ®Google Scholar
• Prijovich ZM, Burnouf PA, Chou HC, et al. Synthesis and antitumor properties of BQC-glucuronide, a camptothecin prodrug for selective tumor activation. Mol Pharm. 2016 Apr;13(4):1242–1250. DOI:10.1021/acs.molpharmaceut.5b00771
   PubMed Web of Science ®Google Scholar
• Bensalma S, Chadeneau C, Legigan T, et al. Evaluation of cytotoxic properties of a cyclopamine glucuronide prodrug in rat glioblastoma cells and tumors. J Mol Neurosci. 2015 Jan;55(1):51–61. DOI:10.1007/s12031-014-0395-3
   PubMed Web of Science ®Google Scholar
• Legigan T, Clarhaut J, Renoux B, et al. Synthesis and biological evaluations of a monomethylauristatin E glucuronide prodrug for selective cancer chemotherapy. Eur J Med Chem. 2013 Sep;67:75–80.
   PubMed Web of Science ®Google Scholar
• Chen KC, Schmuck K, Tietze LF, et al. Selective cancer therapy by extracellular activation of a highly potent glycosidic duocarmycin analogue. Mol Pharm. 2013 May 6;10(5):1773–1782. DOI:10.1021/mp300581u
   PubMed Web of Science ®Google Scholar
• Biela BH, Khawli LA, Hu P, et al. Chimeric TNT-3/human beta-glucuronidase fusion proteins for antibody-directed enzyme prodrug therapy (ADEPT). Cancer Biother Radiopharm. 2003 Jun;18(3):339–353. DOI:10.1089/108497803322285099
   PubMed Web of Science ®Google Scholar
• Chen KC, Wu SY, Leu YL, et al. A humanized immunoenzyme with enhanced activity for glucuronide prodrug activation in the tumor microenvironment. Bioconjug Chem. 2011 May 18;22(5):938–948. DOI:10.1021/bc1005784 .
   PubMed Web of Science ®Google Scholar
• Thomas M, Clarhaut J, Tranoy-Opalinski I, et al. Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy. Bioorg Med Chem. 2008 Sep 1;16(17):8109–8116.
   PubMed Web of Science ®Google Scholar
• Kamal A, Tekumalla V, Krishnan A, et al. Development of pyrrolo[2,1-c][1,4]benzodiazepine beta-galactoside prodrugs for selective therapy of cancer by ADEPT and PMT. ChemMedChem. 2008 May;3(5):794–802. DOI:10.1002/cmdc.200700328
   PubMed Web of Science ®Google Scholar
• Leu YL, Chen CS, Wu YJ, et al. Benzyl ether-linked glucuronide derivative of 10-hydroxycamptothecin designed for selective camptothecin-based anticancer therapy. J Med Chem. 2008 Mar 27;51(6):1740–1746.
   PubMed Web of Science ®Google Scholar
• Alaoui AE, Saha N, Schmidt F, et al. New Taxol (paclitaxel) prodrugs designed for ADEPT and PMT strategies in cancer chemotherapy. Bioorg Med Chem. 2006 Jul 15;14(14):5012–5019.
   PubMed Web of Science ®Google Scholar
• Kerr DE, Schreiber GJ, Vrudhula VM, et al. Regressions and cures of melanoma xenografts following treatment with monoclonal antibody beta-lactamase conjugates in combination with anticancer prodrugs. Cancer Res. 1995 Aug 15;55(16):3558–3563.
   PubMed Web of Science ®Google Scholar
• Haisma HJ, Boven E, van Muijen M, et al. A monoclonal antibody-beta-glucuronidase conjugate as activator of the prodrug epirubicin-glucuronide for specific treatment of cancer. Br J Cancer. 1992 Sep;66(3):474–478.
   PubMed Web of Science ®Google Scholar
• Svensson HP, Kadow JF, Vrudhula VM, et al. Monoclonal antibody-beta-lactamase conjugates for the activation of a cephalosporin mustard prodrug. Bioconjug Chem. 1992 Mar–Apr;3(2):176–181.
   PubMed Web of Science ®Google Scholar
• Meyer DL, Jungheim LN, Law KL, et al. Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models. Cancer Res. 1993 Sep 1;53(17):3956–3963.
   PubMed Web of Science ®Google Scholar
• Vrudhula VM, Svensson HP, Senter PD. Cephalosporin derivatives of doxorubicin as prodrugs for activation by monoclonal antibody-beta-lactamase conjugates. J Med Chem. 1995 Apr 14;38(8):1380–1385.
   PubMed Web of Science ®Google Scholar
• Rodrigues ML, Carter P, Wirth C, et al. Synthesis and beta-lactamase-mediated activation of a cephalosporin-taxol prodrug. Chem Biol. 1995 Apr;2(4):223–227.
   PubMedGoogle Scholar
• Vrudhula VM, Svensson HP, Senter PD. Immunologically specific activation of a cephalosporin derivative of mitomycin C by monoclonal antibody beta-lactamase conjugates. J Med Chem. 1997 Aug 15;40(17):2788–2792.
   PubMed Web of Science ®Google Scholar
• Siemers NO, Kerr DE, Yarnold S, et al. Construction, expression, and activities of L49-sFv-beta-lactamase, a single-chain antibody fusion protein for anticancer prodrug activation. Bioconjug Chem. 1997 Jul–Aug;8(4):510–519. DOI:10.1021/bc9700751
   PubMed Web of Science ®Google Scholar
• Vrudhula VM, Kerr DE, Siemers NO, et al. Cephalosporin prodrugs of paclitaxel for immunologically specific activation by L-49-sFv-beta-lactamase fusion protein. Bioorg Med Chem Lett. 2003 Feb 10;13(3):539–542.
   PubMed Web of Science ®Google Scholar
• Phelan RM, Ostermeier M, Townsend CA. Design and synthesis of a beta-lactamase activated 5-fluorouracil prodrug. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1261–1263.
   PubMed Web of Science ®Google Scholar
• Zhou X, Wang H, Shi P, et al. Characterization of a fusion protein of RGD4C and the beta-lactamase variant for antibody-directed enzyme prodrug therapy. Onco Targets Ther. 2014;7:535–541.
   PubMed Web of Science ®Google Scholar
• Danks MK, Yoon KJ, Bush RA, et al. Tumor-targeted enzyme/prodrug therapy mediates long-term disease-free survival of mice bearing disseminated neuroblastoma. Cancer Res. 2007 Jan 1;67(1):22–25.
   PubMed Web of Science ®Google Scholar
• Smith GK, Banks S, Blumenkopf TA, et al. Toward antibody-directed enzyme prodrug therapy with the T268G mutant of human carboxypeptidase A1 and novel in vivo stable prodrugs of methotrexate. J Biol Chem. 1997 Jun 20;272(25):15804–15816.
   PubMed Web of Science ®Google Scholar
• Hao XK, Liu JY, Yue QH, et al. In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein. Prostate. 2006 Jun 1;66(8):858–866.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer. Expert Rev Anticancer Ther. 2006 Oct;6(10):1421–1431. DOI:10.1586/14737140.6.10.1421
   PubMed Web of Science ®Google Scholar
• Dowell RI, Springer CJ, Davies DH, et al. New mustard prodrugs for antibody-directed enzyme prodrug therapy: alternatives to the amide link. J Med Chem. 1996 Mar 1;39(5):1100–1105.
   PubMed Web of Science ®Google Scholar
• Panjideh H, Da Silva Coelho VC, Dernedde J, et al. Biodistribution and efficacy of [131I]A33scFv:: CDy,a recombinant antibody-enzyme protein for colon cancer. Int J Oncol. 2008 Apr;32(4):925–930.
   PubMed Web of Science ®Google Scholar
• Bonifert G, Folkes L, Gmeiner C, et al. Recombinant horseradish peroxidase variants for targeted cancer treatment. Cancer Med. Jun;5(6):1194–1203. DOI:10.1002/cam4.668
   PubMed Web of Science ®Google Scholar
• Mauger AB, Burke PJ, Somani HH, et al. Self-immolative prodrugs: candidates for antibody-directed enzyme prodrug therapy in conjunction with a nitroreductase enzyme. J Med Chem. 1994 Oct 14;37(21):3452–3458.
   PubMed Web of Science ®Google Scholar
• Hay MP, Sykes BM, Denny WA, et al. A 2-nitroimidazole carbamate prodrug of 5-amimo-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbony l]-1,2-dihydro-3H–benz[E]indole (amino-seco-CBI-TMI) for use with ADEPT and GDEPT. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2237–2242.
   PubMed Web of Science ®Google Scholar
• Knox RJ, Friedlos F, Boland MP. The bioactivation of CB 1954 and its use as a prodrug in antibody-directed enzyme prodrug therapy (ADEPT). Cancer Metastasis Rev. 1993 Jun;12(2):195–212.
   PubMed Web of Science ®Google Scholar
• Sagnou MJ, Howard PW, Gregson SJ, et al. Design and synthesis of novel pyrrolobenzodiazepine (PBD) prodrugs for ADEPT and GDEPT. Bioorg Med Chem Lett. 2000 Sep 18;10(18):2083–2086.
   PubMed Web of Science ®Google Scholar
• Bignami GS, Senter PD, Grothaus PG, et al. N-(4ʹ-hydroxyphenylacetyl)palytoxin: a palytoxin prodrug that can be activated by a monoclonal antibody-penicillin G amidase conjugate. Cancer Res. 1992 Oct 15;52(20):5759–5764.
   PubMed Web of Science ®Google Scholar
• Vrudhula VM, Senter PD, Fischer KJ, et al. Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate. J Med Chem. 1993 Apr 2;36(7):919–923.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Xiang G, Zhang Y, et al. Increase of doxorubicin sensitivity for folate receptor positive cells when given as the prodrug N-(phenylacetyl) doxorubicin in combination with folate-conjugated PGA. J Pharm Sci. 2006 Oct;95(10):2266–2275. DOI:10.1002/jps.20714
   PubMed Web of Science ®Google Scholar
• Gopin A, Ebner S, Attali B, et al. Enzymatic activation of second-generation dendritic prodrugs: conjugation of self-immolative dendrimers with poly(ethylene glycol) via click chemistry. Bioconjug Chem. 2006 Nov–Dec;17(6):1432–1440. DOI:10.1021/bc060180n
   PubMed Web of Science ®Google Scholar
• Kerr DE, Senter PD, Burnett WV, et al. Antibody-penicillin-V-amidase conjugates kill antigen-positive tumor cells when combined with doxorubicin phenoxyacetamide. Cancer Immunol Immunother. 1990;31(4):202–206.
   PubMed Web of Science ®Google Scholar
• Afshar S, Asai T, Morrison SL. Humanized ADEPT comprised of an engineered human purine nucleoside phosphorylase and a tumor targeting peptide for treatment of cancer. Mol Cancer Ther. 2009 Jan;8(1):185–193. DOI:10.1158/1535-7163.MCT-08-0652
   PubMed Web of Science ®Google Scholar
• Kaul S, Igwemezie LN, Stewart DJ, et al. Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors. J Clin Oncol. 1995 Nov;13(11):2835–2841.
   PubMed Web of Science ®Google Scholar
• Tozer TN, Rigod J, McLeod AD, et al. Colon-specific delivery of dexamethasone from a glucoside prodrug in the guinea pig. Pharm Res. 1991 Apr;8(4):445–454.
   PubMed Web of Science ®Google Scholar
• Roffler SR, Wang SM, Chern JW, et al. Anti-neoplastic glucuronide prodrug treatment of human tumor cells targeted with a monoclonal antibody-enzyme conjugate. Biochem Pharmacol. 1991 Oct 24;42(10):2062–2065.
   PubMed Web of Science ®Google Scholar
• Bosslet K, Czech J, Lorenz P, et al. Molecular and functional characterisation of a fusion protein suited for tumour specific prodrug activation. Br J Cancer. 1992 Feb;65(2):234–238.
   PubMed Web of Science ®Google Scholar
• Bosslet K, Czech J, Hoffmann D. Tumor-selective prodrug activation by fusion protein-mediated catalysis. Cancer Res. 1994 Apr 15;54(8):2151–2159.
   PubMed Web of Science ®Google Scholar
• de Graaf M, Boven E, Oosterhoff D, et al. A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug. Br J Cancer. 2002 Mar 4;86(5):811–818. DOI:10.1038/sj.bjc.6600143
   PubMed Web of Science ®Google Scholar
• Tranoy-Opalinski I, Legigan T, Barat R, et al. beta-Glucuronidase-responsive prodrugs for selective cancer chemotherapy: an update. Eur J Med Chem. 2014 Mar 3;74:302–313.
   PubMed Web of Science ®Google Scholar
• Wang H, Zhou XL, Long W, et al. A fusion protein of RGD4C and beta-lactamase has a favorable targeting effect in its use in antibody directed enzyme prodrug therapy. Int J Mol Sci. 2015;16(5):9625–9634. DOI:10.3390/ijms16059625
   PubMed Web of Science ®Google Scholar
• Wallace PM, MacMaster JF, Smith VF, et al. Intratumoral generation of 5-fluorouracil mediated by an antibody-cytosine deaminase conjugate in combination with 5-fluorocytosine. Cancer Res. 1994 May 15;54(10):2719–2723.
   PubMed Web of Science ®Google Scholar
• Modlin IM, Lawton GP, Tang LH, et al. The mastomys gastric carcinoid: aspects of enterochromaffin-like cell function. Digestion. 1994;55(Suppl 3):31–37.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD. The first bagshawe lecture. Towards generating cytotoxic agents at cancer sites. Br J Cancer. 1989 Sep;60(3):275–281.
   PubMed Web of Science ®Google Scholar
• Kerr DE, Li Z, Siemers NO, et al. Development and activities of a new melphalan prodrug designed for tumor-selective activation. Bioconjug Chem. 1998 Mar–Apr;9(2):255–259. DOI:10.1021/bc970163l
   PubMed Web of Science ®Google Scholar
• Alderson RF, Toki BE, Roberge M, et al. Characterization of a CC49-based single-chain fragment-beta-lactamase fusion protein for antibody-directed enzyme prodrug therapy (ADEPT). Bioconjug Chem. 2006 Mar–Apr;17(2):410–418. DOI:10.1021/bc0503521
   PubMed Web of Science ®Google Scholar
• Harding FA, Liu AD, Stickler M, et al. A beta-lactamase with reduced immunogenicity for the targeted delivery of chemotherapeutics using antibody-directed enzyme prodrug therapy. Mol Cancer Ther. 2005 Nov;4(11):1791–1800. DOI:10.1158/1535-7163.MCT-05-0189 .
   PubMed Web of Science ®Google Scholar
• Osipovitch DC, Parker AS, Makokha CD, et al. Design and analysis of immune-evading enzymes for ADEPT therapy. Protein Eng Des Sel. 2012 Oct;25(10):613–623. DOI:10.1093/protein/gzs044 .
   PubMed Web of Science ®Google Scholar
• Sherwood RF, Melton RG, Alwan SM, et al. Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method. Eur J Biochem. 1985 May 2;148(3):447–453.
   PubMedGoogle Scholar
• Melton RG, Searle F, Sherwood RF, et al. The potential of carboxypeptidase G2: antibody conjugates as anti-tumour agents. II. In vivo localising and clearance properties in a choriocarcinoma model. Br J Cancer. 1990 Mar;61(3):420–424.
   PubMed Web of Science ®Google Scholar
• Frei E 3rd, Teicher BA, Holden SA, et al. Preclinical studies and clinical correlation of the effect of alkylating dose. Cancer Res. 1988 Nov 15;48(22):6417–6423.
   PubMed Web of Science ®Google Scholar
• Springer CJ, Antoniw P, Bagshawe KD, et al. Novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase G2. J Med Chem. 1990 Feb;33(2):677–681.
   PubMed Web of Science ®Google Scholar
• Brindley CJ, Pedley RB, Antoniw P, et al. Activity and distribution studies of etoposide and mitozolomide in vivo and in vitro against human choriocarcinoma cell lines. Cancer Chemother Pharmacol. 1987;19(3):221–225.
   PubMed Web of Science ®Google Scholar
• Springer CJ, Bagshawe KD, Sharma SK, et al. Ablation of human choriocarcinoma xenografts in nude mice by antibody-directed enzyme prodrug therapy (ADEPT) with three novel compounds. Eur J Cancer. 1991;27(11):1361–1366.
   PubMed Web of Science ®Google Scholar
• Sharma SK, Bagshawe KD, Burke PJ, et al. Inactivation and clearance of an anti-CEA carboxypeptidase G2 conjugate in blood after localisation in a xenograft model. Br J Cancer. 1990 May;61(5):659–662.
   PubMed Web of Science ®Google Scholar
• Thornburg RW, Day JF, Baynes JW, et al. Carbohydrate-mediated clearance of immune complexes from the circulation. A role for galactose residues in the hepatic uptake of IgG-antigen complexes. J Biol Chem. 1980 Jul 25;255(14):6820–6825.
   PubMed Web of Science ®Google Scholar
• Sharma SK, Bagshawe KD, Springer CJ, et al. Antibody directed enzyme prodrug therapy (ADEPT): a three phase system. Dis Markers. 1991 May-Aug;9(3–4):225–231.
   PubMed Web of Science ®Google Scholar
• Sharma SK, Boden JA, Springer CJ, et al. Antibody-directed enzyme prodrug therapy (ADEPT). A three-phase study in ovarian tumor xenografts. Cell Biophys. 1994;24-25:219–228.
   PubMedGoogle Scholar
• Eccles SA, Court WJ, Box GA, et al. Regression of established breast carcinoma xenografts with antibody-directed enzyme prodrug therapy against c-erbB2 p185. Cancer Res. 1994 Oct 1;54(19):5171–5177.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD, Sharma SK, Springer CJ, et al. Antibody directed enzyme prodrug therapy (ADEPT): clinical report. Dis Markers. 1991 May–Aug;9(3–4):233–238.
   PubMed Web of Science ®Google Scholar
• Bagshawe KD, Sharma SK, Springer CJ, et al. Antibody directed enzyme prodrug therapy: a pilot scale clinical trial. Tumor Targeting. 1995;1:17–29.
   Google Scholar
• Napier MP, Sharma SK, Springer CJ, et al. Antibody-directed enzyme prodrug therapy: efficacy and mechanism of action in colorectal carcinoma. Clin Cancer Res. 2000 Mar;6(3):765–772.
   PubMed Web of Science ®Google Scholar
• Francis RJ, Sharma SK, Springer C, et al. A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours. Br J Cancer. 2002 Sep 9;87(6):600–607. DOI:10.1038/sj.bjc.6600517 .
   PubMed Web of Science ®Google Scholar
• Mayer A, Francis RJ, Sharma SK, 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. 2006 Nov 1;12(21):6509–6516. DOI:10.1158/1078-0432.CCR-06-0769 .
   PubMed Web of Science ®Google Scholar
• Wilkins D, Mayer A, Sharma S, et al. Evidence of efficacy of antibody directed enzyme prodrug therapy (ADEPT) in a phase 1 trial in patients with advanced caecinoma. AACR Meet Abstr. 2008;LB–200.
   Google Scholar
• Bagshawe KD, Sharma SK. Cyclosporine delays host immune response to antibody enzyme conjugate in ADEPT. Transplant Proc. 1996 Dec;28(6):3156–3158.
   PubMed Web of Science ®Google Scholar
• Springer CJ, Poon GK, Sharma SK, et al. Identification of prodrug, active drug, and metabolites in an ADEPT clinical study. Cell Biophys. 1993 Jan–Jun;22(1–3):9–26.
   PubMedGoogle Scholar
• Bagshawe KD. Antibody-directed enzyme prodrug therapy (ADEPT). Adv Pharmacol. 1993;24:99–121.
   PubMedGoogle Scholar
• Sharma SK, Bagshawe KD, Melton RG, et al. Human immune response to monoclonal antibody-enzyme conjugates in ADEPT pilot clinical trial. Cell Biophys. 1992 Aug–Dec;21(1–3):109–120. DOI:10.1007/BF02789482
   PubMedGoogle Scholar
• Martin J, Stribbling SM, Poon GK, et al. Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial. Cancer Chemother Pharmacol. 1997;40(3):189–201. DOI:10.1007/s002800050646
   PubMed Web of Science ®Google Scholar
• Springer CJ, Dowell R, Burke PJ, 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. 1995 Dec 22;38(26):5051–5065.
   PubMed Web of Science ®Google Scholar
• Blakey DC, Burke PJ, Davies DH, et al. ZD2767, an improved system for antibody-directed enzyme prodrug therapy that results in tumor regressions in colorectal tumor xenografts. Cancer Res. 1996 Jul 15;56(14):3287–3292.
   PubMed Web of Science ®Google Scholar
• Monks NR, Blakey DC, East SJ, et al. DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767. Eur J Cancer. 2002 Jul;38(11):1543–1552.
   PubMed Web of Science ®Google Scholar
• Melton RG, Boyle JM, Rogers GT, et al. Optimisation of small-scale coupling of A5B7 monoclonal antibody to carboxypeptidase G2. J Immunol Methods. 1993 Jan 14;158(1):49–56.
   PubMed Web of Science ®Google Scholar
• Chester KA, Begent RH, Robson L, et al. Phage libraries for generation of clinically useful antibodies. Lancet. 1994 Feb 19;343(8895):455–456.
   PubMed Web of Science ®Google Scholar
• Michael NP, Chester KA, Melton RG, et al. In vitro and in vivo characterisation of a recombinant carboxypeptidase G2:: anti-CEAscFv fusion protein. Immunotechnology. 1996 Feb;2(1):47–57.
   PubMedGoogle Scholar
• Bhatia J, Sharma SK, Chester KA, et al. Catalytic activity of an in vivo tumor targeted anti-CEA scFv:: carboxypeptidaseG2 fusion protein. Int J Cancer. 2000 Feb 15;85(4):571–577.
   PubMed Web of Science ®Google Scholar
• Medzihradszky KF, Spencer DI, Sharma SK, et al. Glycoforms obtained by expression in Pichia pastoris improve cancer targeting potential of a recombinant antibody-enzyme fusion protein. Glycobiology. 2004 Jan;14(1):27–37. DOI:10.1093/glycob/cwh001
   PubMed Web of Science ®Google Scholar
• Sharma SK, Pedley RB, Bhatia J, 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. 2005 Jan 15;11(2 Pt 1):814–825.
   PubMed Web of Science ®Google Scholar
• Tolner B, Smith L, Begent RH, et al. Production of recombinant protein in Pichia pastoris by fermentation. Nat Protoc. 2006;1(2):1006–1021. DOI:10.1038/nprot.2006.126 .
   PubMed Web of Science ®Google Scholar
• Tolner B, Smith L, Begent RH, et al. Expanded-bed adsorption immobilized-metal affinity chromatography. Nat Protoc. 2006;1(3):1213–1222. DOI:10.1038/nprot.2006.127 .
   PubMed Web of Science ®Google Scholar
• Pedley RB, Sharma SK, Boxer GM, et al. Enhancement of antibody-directed enzyme prodrug therapy in colorectal xenografts by an antivascular agent. Cancer Res. 1999 Aug 15;59(16):3998–4003.
   PubMed Web of Science ®Google Scholar
• Pedley RB, Hill SA, Boxer GM, et al. Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate. Cancer Res. 2001 Jun 15;61(12):4716–4722.
   PubMed Web of Science ®Google Scholar
• Meyer T, Gaya AM, Dancey G, et al. A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas. Clin Cancer Res. 2009 Jul 1;15(13):4484–4492.
   PubMed Web of Science ®Google Scholar
• Webley SD, Francis RJ, Pedley RB, et al. Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material. Br J Cancer. 2001 Jun 15;84(12):1671–1676.
   PubMed Web of Science ®Google Scholar
• Gavande NS, VanderVere-Carozza PS, Hinshaw HD, et al. DNA repair targeted therapy: the past or future of cancer treatment? Pharmacol Ther. 2016 Apr;160:65–83.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Ashworth A. Targeted therapy for cancer using PARP inhibitors. Curr Opin Pharmacol. 2008 Aug;8(4):363–369. DOI:10.1016/j.coph.2008.06.016
   PubMed Web of Science ®Google Scholar
• Drew Y. The development of PARP inhibitors in ovarian cancer: from bench to bedside. Br J Cancer. 2015 Dec 15;113(Suppl 1):SS3–SS9.
   PubMed Web of Science ®Google Scholar
• Yasukawa M, Fujihara H, Fujimori H, et al. Synergetic effects of PARP inhibitor AZD2281 and cisplatin in oral squamous cell carcinoma in vitro and in vivo. Int J Mol Sci. 2016;17(3):272.
   PubMed Web of Science ®Google Scholar
• Jang NY, Kim DH, Cho BJ, et al. Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer. BMC Cancer. 2015;15:89. DOI:10.1186/s12885-015-1090-7.
   PubMed Web of Science ®Google Scholar
• Menezes K, Shahbakhti H, Datta R, et al. PARP inhibitors augment antibody directed enzyme prodrug therapy. NCRI Cancer Conf Abstr. 2013;B54.
   Google Scholar
• Durisova K, Salovska B, Pejchal J, et al. Chemical inhibition of DNA repair kinases as a promising tool in oncology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(1):11–19.
   PubMed Web of Science ®Google Scholar
• Ciszewski WM, Tavecchio M, Dastych J, et al. DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin. Breast Cancer Res Treat. 2014 Jan;143(1):47–55. DOI:10.1007/s10549-013-2785-6
   PubMed Web of Science ®Google Scholar
• Li X, Tian J, Bo Q, et al. Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63. Tumour Biol. 2015 Dec;36(12):9365–9372. DOI:10.1007/s13277-015-3642-5
   PubMed Web of Science ®Google Scholar
• Sharma SK, Rose-Hartwell S, Shahbakhti H, et al. Synergistic combination of ADEPT and a DNA-PK inhibitor in human pancreatic cancer cell lines. NCRI Cancer Conf Abstr. 2015;A260.
   Google Scholar
• Chuang KH, Cheng CM, Roffler SR, et al. Combination cancer therapy by hapten-targeted prodrug-activating enzymes and cytokines. Bioconjug Chem. 2006 May–Jun;17(3):707–714. DOI:10.1021/bc0600160 .
   PubMed Web of Science ®Google Scholar
• Honeychurch J, Cheadle EJ, Dovedi SJ, et al. Immuno-regulatory antibodies for the treatment of cancer. Expert Opin Biol Ther. 2015 Jun;15(6):787–801. DOI:10.1517/14712598.2015.1036737 .
   PubMed Web of Science ®Google Scholar
• Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273–290. DOI:10.1038/nrclinonc.2016.25 .
   PubMed Web of Science ®Google Scholar
• Chen BM, Cheng TL, Tzou SC, et al. Potentiation of antitumor immunity by antibody-directed enzyme prodrug therapy. Int J Cancer. 2001 Dec 15; 94(6):850–858.
   PubMed Web of Science ®Google Scholar
• Spencer DI, Robson L, Purdy D, et al. A strategy for mapping and neutralizing conformational immunogenic sites on protein therapeutics. Proteomics. 2002 Mar;2(3):271–279.
   PubMed Web of Science ®Google Scholar
• Mayer A, Sharma SK, Tolner B, 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 Cancer. 2004 Jun 14;90(12):2402–2410. DOI:10.1038/sj.bjc.6601888 .
   PubMed Web of Science ®Google Scholar
• Sharma S, Griffin N, Cleverly S, et al. Evidence that hexa-histidine tags on therapeutic proteins are not immunogenic in patients. NCRI Cancer Conf Abstr. 2009;C117.
   Google Scholar
• Baker MP, Jones TD. Identification and removal of immunogenicity in therapeutic proteins. Curr Opin Drug Discov Devel. 2007 Mar;10(2):219–227.
   PubMedGoogle Scholar
• Chester KA, Baker M, Mayer A. Overcoming the immunologic response to foreign enzymes in cancer therapy. Expert Rev Clin Immunol. 2005 Nov;1(4):549–559. DOI:10.1586/1744666X.1.4.549
   PubMedGoogle Scholar
• Jones TD, Crompton LJ, Carr FJ, et al. Deimmunization of monoclonal antibodies. Methods Mol Biol. 2009;525:405–23, xiv. DOI:10.1007/978-1-59745-554-1_21
   PubMedGoogle Scholar
• Entwistle J, Brown JG, Chooniedass S, et al. Preclinical evaluation of VB6-845: an anti-EpCAM immunotoxin with reduced immunogenic potential. Cancer Biother Radiopharm. 2012 Nov;27(9):582–592. DOI:10.1089/cbr.2012.1200.271
   PubMed Web of Science ®Google Scholar
• Deckert PM, Bornmann WG, Ritter G, et al. Specific tumour localisation of a huA33 antibody–carboxypeptidase A conjugate and activation of methotrexate-phenylalanine. Int J Oncol. 2004 May;24(5):1289–1295.
   PubMed Web of Science ®Google Scholar
• Andrady C, Sharma SK, Chester KA. Antibody-enzyme fusion proteins for cancer therapy. Immunotherapy. 2011 Feb;3(2):193–211. DOI:10.2217/imt.10.90
   PubMed Web of Science ®Google Scholar
• de Graaf M, Boven E, Scheeren HW, et al. Beta-glucuronidase-mediated drug release. Curr Pharm Des. 2002;8(15):1391–1403.
   PubMed Web of Science ®Google Scholar
• Nishi Y. Enzyme/abzyme prodrug activation systems: potential use in clinical oncology. Curr Pharm Des. 2003;9(26):2113–2130.
   PubMed Web of Science ®Google Scholar
• Wentworth P, Datta A, Blakey D, et al. Toward antibody-directed “abzyme” prodrug therapy, ADAPT: carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing. Proc Natl Acad Sci USA. 1996 Jan 23; 93(2):799–803.
   PubMed Web of Science ®Google Scholar
• Shabat D, Lode HN, Pertl U, et al. In vivo activity in a catalytic antibody-prodrug system: antibody catalyzed etoposide prodrug activation for selective chemotherapy. Proc Natl Acad Sci USA. 2001 Jun 19;98(13):7528–7533.
   PubMed Web of Science ®Google Scholar
• Kakinuma H, Fujii I, Nishi Y. Selective chemotherapeutic strategies using catalytic antibodies: a common pro-moiety for antibody-directed abzyme prodrug therapy. J Immunol Methods. 2002 Nov 1;269(1–2):269–281.
   PubMed Web of Science ®Google Scholar
• Abraham S, Guo F, Li LS, et al. Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation. Proc Natl Acad Sci USA. 2007 Mar 27;104(13):5584–5589.
   PubMed Web of Science ®Google Scholar
• Ramya LN, Pulicherla KK. Studies on deimmunization of antileukaemic L-asparaginase to have reduced clinical immunogenicity–An in silico approach. Pathol Oncol Res. 2015 Sep;21(4):909–920. DOI:10.1007/s12253-015-9912-0
   PubMed Web of Science ®Google Scholar
• Dziubla TD, Karim A, Muzykantov VR. Polymer nanocarriers protecting active enzyme cargo against proteolysis. J Control Release. 2005 Feb 2;102(2):427–439.
   PubMed Web of Science ®Google Scholar
• Slowing II, Vivero-Escoto JL, Wu CW, et al. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev. 2008 Aug 17;60(11):1278–1288.
   PubMed Web of Science ®Google Scholar
• Ortac I, Simberg D, Yeh YS, et al. Dual-porosity hollow nanoparticles for the immunoprotection and delivery of nonhuman enzymes. Nano Lett. 2014 Jun 11;14(6):3023–3032. DOI:10.1021/nl404360k .
   PubMed Web of Science ®Google Scholar
• Chen KC, Wu CH, Chang CY, et al. Directed evolution of a lysosomal enzyme with enhanced activity at neutral pH by mammalian cell-surface display. Chem Biol. 2008 Dec 22;15(12):1277–1286.
   PubMedGoogle Scholar
• Shukla GS, Krag DN. Novel beta-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy. J Drug Target. 2010 Feb;18(2):115–124. DOI:10.3109/10611860903244181
   PubMed Web of Science ®Google Scholar
• Copp JN, Williams EM, Rich MH, et al. Toward a high-throughput screening platform for directed evolution of enzymes that activate genotoxic prodrugs. Protein Eng Des Sel. 2014 Oct;27(10):399–403. DOI:10.1093/protein/gzu025
   PubMed Web of Science ®Google Scholar
• Kuah E, Toh S, Yee J, et al. Enzyme mimics: advances and applications. Chemistry. 2016 Apr 8; 22(25):8404–8430.
   PubMed Web of Science ®Google Scholar
• Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014;16(2):209 .
   PubMed Web of Science ®Google Scholar
• Marrone KA, Ying W, Naidoo J. Immune-related adverse events from immune checkpoint inhibitors. Clin Pharmacol Ther. 2016 May 12;100(3):242–251.
   PubMed Web of Science ®Google Scholar
• Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375–2391.
   PubMed Web of Science ®Google Scholar
• Tietze LF, Schmuck K, Schuster HJ, et al. Synthesis and biological evaluation of prodrugs based on the natural antibiotic duocarmycin for use in ADEPT and PMT. Chemistry. 2011 Feb 7;17(6):1922–1929. DOI:10.1002/chem.201002798 .
   PubMed Web of Science ®Google Scholar
• Cheng TL, Chen BM, Chern JW, et al. Efficient clearance of poly(ethylene glycol)-modified immunoenzyme with anti-PEG monoclonal antibody for prodrug cancer therapy. Bioconjug Chem. 2000 Mar–Apr;11(2):258–266.
   PubMed Web of Science ®Google Scholar
• Zhang X, Wang H, Ma Z, et al. Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns. Expert Opin Drug Metab Toxicol. 2014 Dec;10(12):1691–1702. DOI:10.1517/17425255.2014.967679
   PubMed Web of Science ®Google Scholar
• Cortez-Retamozo V, Backmann N, Senter PD, et al. Efficient cancer therapy with a nanobody-based conjugate. Cancer Res. 2004 Apr 15;64(8):2853–2857.
   PubMed Web of Science ®Google Scholar
• Alix-Panabieres C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016 Mar 11;6(5):479–491.
   PubMed Web of Science ®Google Scholar