全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
Antibodies  2013 

Antibody Drug Conjugates as Cancer Therapeutics

DOI: 10.3390/antib2010113

Keywords: antibody drug conjugate, ADC, immunoconjugate, antibody, cytotoxic, cancer, drug delivery

Full-Text   Cite this paper   Add to My Lib

Abstract:

Monoclonal antibody (MAb) based therapies have achieved considerable success in oncology, primarily when used in combination with cytotoxic drugs. Antibody drug conjugates (ADCs) are a class of therapeutics that harness the antigen-selectivity of MAbs to deliver highly potent cytotoxic drugs to antigen-expressing tumor cells. The use of MAb directed delivery can confer a therapeutic index to highly potent cytotoxic drugs, increasing both the efficacy and safety of therapy. Although simple in concept, to achieve the design goal of improved therapeutic efficacy and reduced toxicity, each of the components of an ADC; the MAb, linker and drug need to considered in the context of the targeted antigen, the selectivity of antigen expression and the biology of the tumor type on which the target antigen is expressed. The characteristics of targets, MAbs, linkers and drugs being used in ADC design are discussed.

References

[1]  Kohler, G.; Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975, 256, 495–497, doi:10.1038/256495a0.
[2]  Carter, P.J. Potent antibody therapeutics by design. Nat. Rev. Immunol. 2006, 6, 343–357, doi:10.1038/nri1837.
[3]  Jakobovits, A. The long-awaited magic bullets: Therapeutic human monoclonal antibodies from transgenic mice. Expert Opin. Investig. Drugs 1998, 7, 607–614, doi:10.1517/13543784.7.4.607.
[4]  Lonberg, N. Human antibodies from transgenic animals. Nat. Biotechnol. 2005, 23, 1117–1125, doi:10.1038/nbt1135.
[5]  Reichert, J.M.; Dhimolea, E. The future of antibodies as cancer drugs. Drug Discov. Today 2012, 17, 954–963, doi:10.1016/j.drudis.2012.04.006.
[6]  Goldenberg, D.M.; Sharkey, R.M. Radioactive antibodies: A historical review of selective targeting and treatment of cancer. Hosp. Pract. (Minneap) 2010, 38, 82–93, doi:10.3810/hp.2010.06.300.
[7]  Steiner, M.; Neri, D. Antibody-radionuclide conjugates for cancer therapy: Historical considerations and new trends. Clin. Cancer Res. 2011, 17, 6406–6416, doi:10.1158/1078-0432.CCR-11-0483.
[8]  Weldon, J.E.; Pastan, I. A guide to taming a toxin—Recombinant immunotoxins constructed from pseudomonas exotoxin A for the treatment of cancer. FEBS J. 2011, 278, 4683–4700, doi:10.1111/j.1742-4658.2011.08182.x.
[9]  Lorberboum-Galski, H. Human toxin-based recombinant immunotoxins/chimeric proteins as a drug delivery system for targeted treatment of human diseases. Expert Opin. Drug Deliv. 2011, 8, 605–621, doi:10.1517/17425247.2011.566269.
[10]  Choudhary, S.; Mathew, M.; Verma, R.S. Therapeutic potential of anticancer immunotoxins. Drug Discov. Today 2011, 16, 495–503, doi:10.1016/j.drudis.2011.04.003.
[11]  Trail, P.A.; Willner, D.; Lasch, S.J.; Henderson, A.J.; Hofstead, S.; Casazza, A.M.; Firestone, R.A.; Hellstrom, I.; Hellstrom, K.E. Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 1993, 261, 212–215.
[12]  Hinman, L.M.; Hamann, P.R.; Wallace, R.; Menendez, A.T.; Durr, F.E.; Upeslacis, J. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: A novel and potent family of antitumor antibiotics. Cancer Res. 1993, 53, 3336–3342.
[13]  Liu, C.; Chari, R.V. The development of antibody delivery systems to target cancer with highly potent maytansinoids. Expert Opin. Investig. Drugs 1997, 6, 169–172, doi:10.1517/13543784.6.2.169.
[14]  Doronina, S.O.; Toki, B.E.; Torgov, M.Y.; Mendelsohn, B.A.; Cerveny, C.G.; Chace, D.F.; DeBlanc, R.L.; Gearing, R.P.; Bovee, T.D.; Siegall, C.B.; et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 2003, 21, 778–784, doi:10.1038/nbt832.
[15]  Trail, P.A.; Bianchi, A.B. Monoclonal antibody drug conjugates in the treatment of cancer. Curr. Opin. Immunol. 1999, 11, 584–588, doi:10.1016/S0952-7915(99)00012-6.
[16]  Dubowchik, G.M.; Walker, M.A. Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs. Pharmacol. Ther. 1999, 83, 67–123, doi:10.1016/S0163-7258(99)00018-2.
[17]  Dubowchik, G.M.; Firestone, R.A.; Padilla, L.; Willner, D.; Hofstead, S.J.; Mosure, K.; Knipe, J.O.; Lasch, S.J.; Trail, P.A. Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: Model studies of enzymatic drug release and antigen-specific in vitro anticancer activity. Bioconjug. Chem. 2002, 13, 855–869.
[18]  Trail, P.A.; King, H.D.; Dubowchik, G.M. Monoclonal antibody drug immunoconjugates for targeted treatment of cancer. Cancer Immunol. Immunother. 2003, 52, 328–337.
[19]  Teicher, B.A. Antibody-drug conjugate targets. Curr. Cancer Drug Targets 2009, 9, 982–1004, doi:10.2174/156800909790192365.
[20]  Blanc, V.; Bousseau, A.; Caron, A.; Carrez, C.; Lutz, R.J.; Lambert, J.M. SAR3419: An anti-CD19-maytansinoid immunoconjugate for the treatment of B-cell malignancies. Clin. Cancer Res. 2011, 17, 6448–6458, doi:10.1158/1078-0432.CCR-11-0485.
[21]  Lewis Phillips, G.D.; Li, G.; Dugger, D.L.; Crocker, L.M.; Parsons, K.L.; Mai, E.; Blattler, W.A.; Lambert, J.M.; Chari, R.V.; Lutz, R.J.; et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008, 68, 9280–9290.
[22]  Petrul, H.M.; Schatz, C.A.; Kopitz, C.C.; Adnane, L.; McCabe, T.J.; Trail, P.; Ha, S.; Chang, Y.S.; Voznesensky, A.; Ranges, G.; et al. Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620 targeting human carbonic anhydrase 9. Mol. Cancer Ther. 2012, 11, 340–349, doi:10.1158/1535-7163.MCT-11-0523.
[23]  Wahl, A.F.; Klussman, K.; Thompson, J.D.; Chen, J.H.; Francisco, L.V.; Risdon, G.; Chace, D.F.; Siegall, C.B.; Francisco, J.A. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002, 62, 3736–3742.
[24]  Barginear, M.F.; John, V.; Budman, D.R. Trastuzumab-DM1: A clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer. Mol. Med. 2012, 18, 1473–1479, doi:10.1007/s00894-011-1172-7.
[25]  Ogura, M.; Hatake, K.; Ando, K.; Tobinai, K.; Tokushige, K.; Ono, C.; Ishibashi, T.; Vandendries, E. Phase I study of anti-CD22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Sci. 2012, 103, 933–938, doi:10.1111/j.1349-7006.2012.02241.x.
[26]  Ricart, A.D. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin. Cancer Res. 2011, 17, 6417–6427, doi:10.1158/1078-0432.CCR-11-0486.
[27]  Verma, S.; Miles, D.; Gianni, L.; Krop, I.E.; Welslau, M.; Baselga, J.; Pegram, M.; Oh, D.Y.; Dieras, V.; Guardino, E.; et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2012, 367, 1783–1791, doi:10.1056/NEJMoa1209124.
[28]  Younes, A.; Bartlett, N.L.; Leonard, J.P.; Kennedy, D.A.; Lynch, C.M.; Sievers, E.L.; Forero-Torres, A. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med. 2010, 363, 1812–1821, doi:10.1056/NEJMoa1002965.
[29]  Younes, A.; Kim, S.; Romaguera, J.; Copeland, A.; Farial Sde, C.; Kwak, L.W.; Fayad, L.; Hagemeister, F.; Fanale, M.; Neelapu, S.; et al. Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma. J. Clin. Oncol. 2012, 30, 2776–2782.
[30]  Gerber, H.P.; Senter, P.D.; Grewal, I.S. Antibody drug-conjugates targeting the tumor vasculature: Current and future developments. MAbs 2009, 1, 247–253, doi:10.4161/mabs.1.3.8515.
[31]  Baccala, A.; Sercia, L.; Li, J.; Heston, W.; Zhou, M. Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology 2007, 70, 385–390, doi:10.1016/j.urology.2007.03.025.
[32]  Haffner, M.C.; Kronberger, I.E.; Ross, J.S.; Sheehan, C.E.; Zitt, M.; Muhlmann, G.; Ofner, D.; Zelger, B.; Ensinger, C.; Yang, X.J.; et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum. Pathol. 2009, 40, 1754–1761, doi:10.1016/j.humpath.2009.06.003.
[33]  Denmeade, S.R.; Mhaka, A.M.; Rosen, D.M.; Brennen, W.N.; Dalrymple, S.; Dach, I.; Olesen, C.; Gurel, B.; Demarzo, A.M.; Wilding, G.; et al. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. Sci. Transl. Med. 2012, 4, 140ra86.
[34]  Katz, J.; Janik, J.E.; Younes, A. Brentuximab vedotin (SGN-35). Clin. Cancer Res. 2011, 17, 6428–6436, doi:10.1158/1078-0432.CCR-11-0488.
[35]  Ikeda, H.; Hideshima, T.; Fulciniti, M.; Lutz, R.J.; Yasui, H.; Okawa, Y.; Kiziltepe, T.; Vallet, S.; Pozzi, S.; Santo, L.; et al. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin. Cancer Res. 2009, 15, 4028–4037, doi:10.1158/1078-0432.CCR-08-2867.
[36]  DeFrancesco, L. Seattle genetics rare cancer drug sails through accelerated approval. Nat. Biotechnol. 2011, 29, 851–852, doi:10.1038/nbt1011-851.
[37]  Jiang, X.R.; Song, A.; Bergelson, S.; Arroll, T.; Parekh, B.; May, K.; Chung, S.; Strouse, R.; Mire-Sluis, A.; Schenerman, M. Advances in the assessment and control of the effector functions of therapeutic antibodies. Nat. Rev. Drug Discov. 2011, 10, 101–111.
[38]  Junttila, T.T.; Li, G.; Parsons, K.; Phillips, G.L.; Sliwkowski, M.X. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res. Treat. 2011, 128, 347–356.
[39]  Kovtun, Y.V.; Goldmacher, V.S. Cell killing by antibody-drug conjugates. Cancer Lett. 2007, 255, 232–240, doi:10.1016/j.canlet.2007.04.010.
[40]  Okeley, N.M.; Miyamoto, J.B.; Zhang, X.; Sanderson, R.J.; Benjamin, D.R.; Sievers, E.L.; Senter, P.D.; Alley, S.C. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin. Cancer Res. 2010, 16, 888–897, doi:10.1158/1078-0432.CCR-09-2069.
[41]  Chari, R.V. Targeted cancer therapy: Conferring specificity to cytotoxic drugs. Acc. Chem. Res. 2008, 41, 98–107, doi:10.1021/ar700108g.
[42]  Doronina, S.O.; Bovee, T.D.; Meyer, D.W.; Miyamoto, J.B.; Anderson, M.E.; Morris-Tilden, C.A.; Senter, P.D. Novel peptide linkers for highly potent antibody-auristatin conjugate. Bioconjug. Chem. 2008, 19, 1960–1963, doi:10.1021/bc800289a.
[43]  Dubowchik, G.M.; Radia, S.; Mastalerz, H.; Walker, M.A.; Firestone, R.A.; Dalton King, H.; Hofstead, S.J.; Willner, D.; Lasch, S.J.; Trail, P.A. Doxorubicin immunoconjugates containing bivalent, lysosomally-cleavable dipeptide linkages. Bioorg. Med. Chem. Lett. 2002, 12, 1529–1532.
[44]  Zhao, R.Y.; Wilhelm, S.D.; Audette, C.; Jones, G.; Leece, B.A.; Lazar, A.C.; Goldmacher, V.S.; Singh, R.; Kovtun, Y.; Widdison, W.C.; et al. Synthesis and evaluation of hydrophilic linkers for antibody-maytansinoid conjugates. J. Med. Chem. 2011, 54, 3606–3623.
[45]  Smyth, M.J.; Pietersz, G.A.; McKenzie, I.F. The mode of action of methotrexate-monoclonal antibody conjugates. Immunol. Cell Biol. 1987, 65, 189–200, doi:10.1038/icb.1987.21.
[46]  Ghose, T.; Ferrone, S.; Blair, A.H.; Kralovec, Y.; Temponi, M.; Singh, M.; Mammen, M. Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen. Cancer Immunol. Immunother. 1991, 34, 90–96, doi:10.1007/BF01741341.
[47]  Elias, D.J.; Kline, L.E.; Robbins, B.A.; Johnson, H.C., Jr.; Pekny, K.; Benz, M.; Robb, J.A.; Walker, L.E.; Kosty, M.; Dillman, R.O. Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma. Am. J. Respir. Crit. Care Med. 1994, 150, 1114–1122.
[48]  Schrappe, M.; Bumol, T.F.; Apelgren, L.D.; Briggs, S.L.; Koppel, G.A.; Markowitz, D.D.; Mueller, B.M.; Reisfeld, R.A. Long-term growth suppression of human glioma xenografts by chemoimmunoconjugates of 4-desacetylvinblastine-3-carboxyhydrazide and monoclonal antibody 9.2.27. Cancer Res. 1992, 52, 3838–3844.
[49]  Petersen, B.H.; DeHerdt, S.V.; Schneck, D.W.; Bumol, T.F. The human immune response to KS1/4-desacetylvinblastine (ly256787) and KS1/4-desacetylvinblastine hydrazide (LY203728) in single and multiple dose clinical studies. Cancer Res. 1991, 51, 2286–2290.
[50]  Yang, H.M.; Reisfeld, R.A. Doxorubicin conjugated with a monoclonal antibody directed to a human melanoma-associated proteoglycan suppresses the growth of established tumor xenografts in nude mice. Proc. Natl. Acad. Sci. USA 1988, 85, 1189–1193, doi:10.1073/pnas.85.4.1189.
[51]  Shih, L.B.; Goldenberg, D.M.; Xuan, H.; Lu, H.W.; Mattes, M.J.; Hall, T.C. Internalization of an intact doxorubicin immunoconjugate. Cancer Immunol. Immunother. 1994, 38, 92–98, doi:10.1007/BF01526203.
[52]  Trail, P.A.; Willner, D.; Lasch, S.J.; Henderson, A.J.; Greenfield, R.S.; King, D.; Zoeckler, M.E.; Braslawsky, G.R. Antigen-specific activity of carcinoma-reactive BR64-doxorubicin conjugates evaluated in vitro and in human tumor xenograft models. Cancer Res. 1992, 52, 5693–5700.
[53]  King, H.D.; Yurgaitis, D.; Willner, D.; Firestone, R.A.; Yang, M.B.; Lasch, S.J.; Hellstrom, K.E.; Trail, P.A. Monoclonal antibody conjugates of doxorubicin prepared with branched linkers: A novel method for increasing the potency of doxorubicin immunoconjugates. Bioconjug. Chem. 1999, 10, 279–288, doi:10.1021/bc980100i.
[54]  King, H.D.; Dubowchik, G.M.; Mastalerz, H.; Willner, D.; Hofstead, S.J.; Firestone, R.A.; Lasch, S.J.; Trail, P.A. Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: Inhibition of aggregation by methoxytriethyleneglycol chains. J. Med. Chem. 2002, 45, 4336–4343.
[55]  Shih, L.B.; Goldenberg, D.M.; Xuan, H.; Lu, H.; Sharkey, R.M.; Hall, T.C. Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier. Cancer Res. 1991, 51, 4192–4198.
[56]  Saleh, M.N.; LoBuglio, A.F.; Trail, P.A. Immunoconjugate Therapy of Solid Tumors: Studies with BR96-Doxorubicin. In Monoclonal Antibody-Based Therapy of Cancer, 1th; Grossbard, M.L., Ed.; Marcel Dekker, Inc: New York, NY, USA, 1998; Volume 15, pp. 397–416.
[57]  Terrett, J.; Gangwar, S.; Rao-Naik, C.; Pan, C.; Guerlavais, V.; Huber, M.; Chong, C.; Green, L.; Cardarelli, P.; King, D.; et al. Single, low dose treatment of lymphoma and renal cancer xenografts with human anti-CD70 antibody-toxin conjugates, results in long term cures. In Proceedings of the 98th Annual Meeting of the American Association for Cancer Research, Los Angeles, CA, USA, 14–18 April 2007.
[58]  Bross, P.F.; Beitz, J.; Chen, G.; Chen, X.H.; Duffy, E.; Kieffer, L.; Roy, S.; Sridhara, R.; Rahman, A.; Williams, G.; et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 2001, 7, 1490–1496.
[59]  Larson, R.A.; Sievers, E.L.; Stadtmauer, E.A.; Lowenberg, B.; Estey, E.H.; Dombret, H.; Theobald, M.; Voliotis, D.; Bennett, J.M.; Richie, M.; et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 2005, 104, 1442–1452, doi:10.1002/cncr.21326.
[60]  Jurcic, J.G. What happened to anti-CD33 therapy for acute myeloid leukemia? Curr. Hematol. Malig. Rep. 2012, 7, 65–73, doi:10.1007/s11899-011-0103-0.
[61]  DiJoseph, J.F.; Dougher, M.M.; Evans, D.Y.; Zhou, B.B.; Damle, N.K. Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-specific immunoconjugate of calicheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP. Cancer Chemother. Pharmacol. 2011, 67, 741–749, doi:10.1007/s00280-010-1342-9.
[62]  Advani, A.; Coiffier, B.; Czuczman, M.S.; Dreyling, M.; Foran, J.; Gine, E.; Gisselbrecht, C.; Ketterer, N.; Nasta, S.; Rohatiner, A.; et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: Results of a phase I study. J. Clin. Oncol. 2010, 28, 2085–2093.
[63]  Cardarelli, P.; King, D.; Terrett, J.; Gangwar, S.; Cohen, L.; Pan, C.; Rao, C.; Deshpande, S.; Angipuram, R.; Passmore, D.; et al. Efficacy and safety of a human anti-CD70 antibody-MGBA conjugate. In Proceedings of the 99th Annual Meeting of the American Association for Cancer Research, San Diego, CA, USA, 12-16 April 2008; AACR: Philadelphia, PA, USA, 2008; p. Abstract nr 4061.
[64]  King, D.; Terrett, J.; Cardarelli, P.; Pan, C.; Rao, C.; Gangwar, S.; Deshpande, S.; Vangipuram, R.; Passmore, D.; Mirjolet, J.; et al. Mechanism of activation of a human anti-CD70 antibody-mgba conjugate and efficacy in a nude rat model of renal carcinoma. In Proceedings of the 99th Annual Meeting of the American Association for Cancer Research, San Diego, CA, USA, 12-16 April 2008; AACR: Philadelphia, PA, USA, 2008; p. Abstract nr 4057.
[65]  Beck, A.; Lambert, J.; Sun, M.; Lin, K. Fourth World Antibody-drug Conjugate Summit: February 29-march 1, 2012, Frankfurt, Germany. MAbs 2012, 4, 637–647, doi:10.4161/mabs.21697.
[66]  Chari, R.V.; Martell, B.A.; Gross, J.L.; Cook, S.B.; Shah, S.A.; Blattler, W.A.; McKenzie, S.J.; Goldmacher, V.S. Immunoconjugates containing novel maytansinoids: Promising anticancer drugs. Cancer Res. 1992, 52, 127–131.
[67]  Oroudjev, E.; Lopus, M.; Wilson, L.; Audette, C.; Provenzano, C.; Erickson, H.; Kovtun, Y.; Chari, R.; Jordan, M.A. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol. Cancer Ther. 2010, 9, 2700–2713, doi:10.1158/1535-7163.MCT-10-0645.
[68]  Mohammad, R.M.; Varterasian, M.L.; Almatchy, V.P.; Hannoudi, G.N.; Pettit, G.R.; Al-Katib, A. Successful treatment of human chronic lymphocytic leukemia xenografts with combination biological agents auristatin PE and bryostatin 1. Clin. Cancer Res. 1998, 4, 1337–1343.
[69]  Doronina, S.O.; Mendelsohn, B.A.; Bovee, T.D.; Cerveny, C.G.; Alley, S.C.; Meyer, D.L.; Oflazoglu, E.; Toki, B.E.; Sanderson, R.J.; Zabinski, R.F.; et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 2006, 17, 114–124, doi:10.1021/bc0502917.
[70]  Francisco, J.A.; Cerveny, C.G.; Meyer, D.L.; Mixan, B.J.; Klussman, K.; Chace, D.F.; Rejniak, S.X.; Gordon, K.A.; DeBlanc, R.; Toki, B.E.; et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 2003, 102, 1458–1465.
[71]  Widdison, W.C.; Wilhelm, S.D.; Cavanagh, E.E.; Whiteman, K.R.; Leece, B.A.; Kovtun, Y.; Goldmacher, V.S.; Xie, H.; Steeves, R.M.; Lutz, R.J.; et al. Semisynthetic maytansine analogues for the targeted treatment of cancer. J. Med. Chem. 2006, 49, 4392–4408.
[72]  de Claro, R.A.; McGinn, K.; Kwitkowski, V.; Bullock, J.; Khandelwal, A.; Habtemariam, B.; Ouyang, Y.; Saber, H.; Lee, K.; Koti, K.; et al. Food and drug administration approval summary: Brentuximab vedotin for the treatment of relapsed Hodgkin lymphoma or relapsed systemic anaplastic large-cell lymphoma. Clin. Cancer Res. 2012, 18, 5845–5849, doi:10.1158/1078-0432.CCR-12-1803.
[73]  Jackson, D.; Gooya, J.; Mao, S.; Kinneer, K.; Xu, L.; Camara, M.; Fazenbaker, C.; Fleming, R.; Swamynathan, S.; Meyer, D.; et al. A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo. Cancer Res. 2008, 68, 9367–9374.
[74]  Oflazoglu, E.; Stone, I.J.; Gordon, K.; Wood, C.G.; Repasky, E.A.; Grewal, I.S.; Law, C.L.; Gerber, H.P. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin. Cancer Res. 2008, 14, 6171–6180.
[75]  Slamon, D.; Eiermann, W.; Robert, N.; Pienkowski, T.; Martin, M.; Press, M.; Mackey, J.; Glaspy, J.; Chan, A.; Pawlicki, M.; et al. Adjuvant trastuzumab in HER2-positive breast cancer. N. Engl. J. Med. 2011, 365, 1273–1283.
[76]  Younes, A.; Yasothan, U.; Kirkpatrick, P. Brentuximab vedotin. Nat. Rev. Drug Discov. 2012, 11, 19–20.
[77]  Hartley, J.A.; Hochhauser, D. Small molecule drugs - optimizing DNA damaging agent-based therapeutics. Curr. Opin. Pharmacol. 2012, 12, 398–402, doi:10.1016/j.coph.2012.03.008.
[78]  Junutula, J.R.; Flagella, K.M.; Graham, R.A.; Parsons, K.L.; Ha, E.; Raab, H.; Bhakta, S.; Nguyen, T.; Dugger, D.L.; Li, G.; et al. Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive breast cancer. Clin. Cancer Res. 2010, 16, 4769–4778, doi:10.1158/1078-0432.CCR-10-0987.
[79]  Sapra, P.; Hooper, A.T.; O'Donnell, C.J.; Gerber, H.P. Investigational antibody drug conjugates for solid tumors. Expert Opin. Investig. Drugs 2011, 20, 1131–1149, doi:10.1517/13543784.2011.582866.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133

WeChat 1538708413