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12 - Monoclonal Antibodies for the Delivery of Cytotoxic Drugs

from PART V - ARMING ANTIBODIES

Published online by Cambridge University Press:  15 December 2009

By
David J. King
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

Monoclonal antibodies have become an established class of anticancer therapeutics over the last few years, and yet there remains a need for increasing their efficacy, especially in solid tumor therapy. For example, trastuzumab, a humanized antibody to human epidermal growth factor receptor type 2 (HER2, ErbB-2 or HER2/neu), is an FDA-approved antibody for treatment of metastatic breast cancer. Trastuzumab therapy of metastatic breast cancer patients who express the HER2 antigen and had progressed after chemotherapy resulted in a 15% overall response rate, with 4% complete responses and a 9.1 month median duration of response. In first-line treatment of metastatic breast cancer the overall response rate increased to 26%, and it is only in combination with chemotherapy that higher response rates have been found. For example, a response rate of 50% was observed when trastuzumab was combined with a standard chemotherapy regimen. A wide variety of different combinations of trastuzumab with chemotherapy have now been explored demonstrating the use of the antibody in combination therapy and trastuzumab remains a valuable therapeutic agent. Nevertheless, results such as these have led to increased interest in improving antibody efficacy, and the use of antibodies directly attached to cytotoxic agents is being widely explored as one means of achieving this. Indeed, trastuzumab itself is now being investigated as an antibody-drug conjugate.

Antibody-mediated delivery of both protein toxins and chemotherapeutic agents has been under investigation for quite some time and even predates the era of monoclonal antibodies.

Type
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Information
Recombinant Antibodies for Immunotherapy , pp. 157 - 173
Publisher: Cambridge University Press
Print publication year: 2009

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References

Cobleigh, MA, Vogel, CL, Tripathy, D, Robert, NJ, Scholl, S, Fehrenbacher, L, Wolter, JM, Paton, V, Shak, S, Lieberman, G, Slamon, DJ (1999). Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17, 2639–2648.CrossRefGoogle ScholarPubMed
Vogel, CL, Cobleigh, MA, Tripathy, D, Gutheil, JC, Harris, LN, Fehrenbacher, L, Slamon, DJ, Murphy, M, Novotny, WF, Burchmore, M, Shak, S, Stewart, SJ, Press, M (2002). Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20, 719–726.CrossRefGoogle ScholarPubMed
Slamon, DJ, Leyland-Jones, B, Shak, S, Fuchs, H, Paton, V, Bajamonde, A, Fleming, T, Eiermann, W, Wolter, J, Pegram, M, Baselga, J, Norton, L (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344, 783–792.CrossRefGoogle Scholar
Hudis, CA (2007). Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med 357, 39–51.CrossRefGoogle ScholarPubMed
Beeram, M, Burris, HA, Modi, S, Birkner, M, Girish, S, Tibbitts, J, Holden, SN, Lutzker, SG, Krop, IE (2008). A phase I study of trastuzumab-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with advanced HER2+ breast cancer (BC). J Clin Oncol 26 (May 20 suppl). 1028.CrossRefGoogle Scholar
Moolten, FL, Cooperband, SR (1970). Selective destruction of target cells by diphtheria toxin conjugated to antibody directed against antigens on the cells. Science 169, 68–70.CrossRefGoogle ScholarPubMed
Hurwitz, E, Levy, R, Maron, R, Wilchek, M, Arnon, R, Sela, M (1975). The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Cancer Res 35, 1175–1181.Google ScholarPubMed
Smyth, MJ, Pietersz, GA, McKenzie, IF (1986). Potentiation of the in vitro cytotoxicity of chlorambucil by monoclonal antibodies. J Immunol 137, 3361–3366.Google ScholarPubMed
Starling, JJ, Maciak, RS, Law, KL, Hinson, NA, Briggs, SL, Laguzza, BC, Johnson, DA (1991). In vivo antitumor activity of a monoclonal antibody-Vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes. Cancer Res 51, 2965–2972.Google ScholarPubMed
Trail, PA, Willner, D, Lasch, SJ, Henderson, AJ, Hofstead, S, Casazza, AM, Firestone, RA, Hellstrom, I, Hellstrom, KE (1993). Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261, 212–215.CrossRefGoogle ScholarPubMed
Starling, JJ, Maciak, RS, Hinson, NA, Nichols, CL, Briggs, SL, Laguzza, BC, Smith, W, Corvalan, JR (1992). In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid immunoconjugates which bind to three distinct epitopes of carcinoembryonic antigen. Bioconjug Chem 3, 315–322.CrossRefGoogle ScholarPubMed
Jain, M, Venkatraman, G, Batra, SK (2007). Optimization of radioimmunotherapy of solid tumors: biological impediments and their modulation. Clin Cancer Res 13, 1374–1382.CrossRefGoogle ScholarPubMed
King, HD, Dubowchik, GM, Mastalerz, H, Willner, D, Hofstead, SJ, Firestone, RA, Lasch, SJ, Trail, PA (2002). Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: inhibition of aggregation by methoxytriethyleneglycol chains. J Med Chem 45, 4336–4343.CrossRefGoogle ScholarPubMed
Sapra, P, Tyagi, P, Allen, TM (2005). Ligand-targeted liposomes for cancer treatment. Curr Drug Deliv 2, 369–381.CrossRefGoogle ScholarPubMed
Hamann, PR, Hinman, LM, Hollander, I, Beyer, CF, Lindh, D, Holcomb, R, Hallett, W, Tsou, HR, Upeslacis, J, Shochat, D, Mountain, A, Flowers, DA, Bernstein, I (2002). Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug Chem 13, 47–58.CrossRefGoogle ScholarPubMed
Petersen, BH, DeHerdt, SV, Schneck, DW, Bumol, TF (1991). The human immune response to KS1/4-desacetylvinblastine (LY256787) and KS1/4-desacetylvinblastine hydrazide (LY203728) in single and multiple dose clinical studies. Cancer Res 51, 2286–2290.Google ScholarPubMed
Salvatore, G, Beers, R, Margulies, I, Kreitman, RJ, Pastan, I (2002). Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. Clin Cancer Res 8, 995–1002.Google ScholarPubMed
Ho, M, Kreitman, RJ, Onda, M, Pastan, I (2005). In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxin. J Biol Chem 280, 607–617.CrossRefGoogle ScholarPubMed
Conner, SD, Schmid, SL (2003). Regulated portals of entry into the cell. Nature 422, 37–44.CrossRefGoogle ScholarPubMed
Recht, LD, Raso, V, Davis, R, Salmonsen, R (1996). Immunotoxin sensitivity of Chinese hamster ovary cells expressing human transferrin receptors with differing internalization rates. Cancer Immunol Immunother 42, 357–361.CrossRefGoogle ScholarPubMed
Ingle, GS, Chan, P, Elliott, JM, Chang, WS, Koeppen, H, Stephan, JP, Scales, SJ (2008). High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate. Br J Haematol 140, 46–58.Google ScholarPubMed
He, D, Yang, H, Lin, Q, Huang, H (2005). Arg9-peptide facilitates the internalization of an anti-CEA immunotoxin and potentiates its specific cytotoxicity to target cells. Int J Biochem Cell Biol 37, 192–205.CrossRefGoogle ScholarPubMed
Law, CL, Cerveny, CG, Gordon, KA, Klussman, K, Mixan, BJ, Chace, DF, Meyer, DL, Doronina, SO, Siegall, CB, Francisco, JA, Senter, PD, Wahl, AF (2004). Efficient elimination of B-lineage lymphomas by anti-CD20-auristatin conjugates. Clin Cancer Res 10, 7842–7851.CrossRefGoogle ScholarPubMed
Austin, CD, Maziere, AM, Pisacane, PI, Dijk, SM, Eigenbrot, C, Sliwkowski, MX, Klumperman, J, Scheller, RH (2004). Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell 15, 5268–5282.CrossRefGoogle ScholarPubMed
Hollander, I, Kunz, A, Hamann, PR (2008). Selection of reaction additives used in the preparation of monomeric antibody-calicheamicin conjugates. Bioconjug Chem 19, 358–361.CrossRefGoogle ScholarPubMed
Doronina, SO, Mendelsohn, BA, Bovee, TD, Cerveny, CG, Alley, SC, Meyer, DL, Oflazoglu, E, Toki, BE, Sanderson, RJ, Zabinski, RF, Wahl, AF, Senter, PD (2006). Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem 17, 114–124.CrossRefGoogle ScholarPubMed
Sutherland, MS, Sanderson, RJ, Gordon, KA, Andreyka, J, Cerveny, CG, Yu, C, Lewis, TS, Meyer, DL, Zabinski, RF, Doronina, SO, Senter, PD, Law, CL, Wahl, AF (2006). Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem 281, 10540–10547.CrossRefGoogle ScholarPubMed
Liu, C, Tadayoni, BM, Bourret, , Mattocks, KM, Derr, SM, Widdison, WC, Kedersha, NL, Ariniello, PD, Goldmacher, VS, Lambert, JM, Blattler, WA, Chari, RV (1996). Eradication of large colon tumor xenografts by targeted delivery of maytansinoids. Proc Natl Acad Sci U S A 93, 8618–8623.CrossRefGoogle ScholarPubMed
Kovtun, YV, Audette, CA, Ye, Y, Xie, H, Ruberti, MF, Phinney SJ, Leece BA, Chittenden, T, Blattler, WA, Goldmacher, VS (2006). Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 66, 3214–3221.CrossRefGoogle ScholarPubMed
Linenberger, ML, Hong, T, Flowers, D, Sievers, EL, Gooley, TA, Bennett, JM, Berger, MS, Leopold, LH, Appelbaum, FR, Bernstein, ID (2001). Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood 98, 988–994.CrossRefGoogle ScholarPubMed
Walter, RB, Gooley, TA, Velden, VH, Loken, MR, Dongen, JJ, Flowers, DA, Bernstein, ID, Appelbaum, FR (2007). CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood 109, 4168–4170.CrossRefGoogle ScholarPubMed
Kartner, N, Evernden-Porelle, D, Bradley, G, Ling, V (1985). Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. Nature 316, 820–823.CrossRefGoogle ScholarPubMed
Naito, K, Takeshita, A, Shigeno, K, Nakamura, S, Fujisawa, S, Shinjo, K, Yoshida, H, Ohnishi, K, Mori, M, Terakawa, S, Ohno, R (2000). Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia 14, 1436–1443.CrossRefGoogle ScholarPubMed
Gomi, K, Kobayashi, E, Miyoshi, K, Ashizawa, T, Okamoto, A, Ogawa, T, Katsumata, S, Mihara, A, Okabe, M, Hirata, T (1992). Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics. Jpn J Cancer Res 83, 113–120.CrossRefGoogle ScholarPubMed
Kobayashi, E, Okamoto, A, Asada, M, Okabe, M, Nagamura, S, Asai, A, Saito, H, Gomi, K, Hirata, T (1994). Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. Cancer Res 54, 2404–2410.Google ScholarPubMed
Pan, C, Gangwar, S, Chen, L, Rao, C, Huber, M, Sattari, P, Do, M, Dai, R, Chong, C, Soderberg, C, Li, H, Sufi, B, Boyd, S, Huang, H, Chen, H, Guerlavais, V, Horgan, K, Sharkov, N, Cardarelli, P, King, DJ (2006). Human antibody conjugates of DNA minor groove-binding alkylating agents with single dose efficacy in xenograft models which retain activity in drug resistant cells. Proc Amer Assoc Cancer Res 47, 1171.Google Scholar
Rao, C, Pan, C, Huber, M, Sattari, P, Chong, C, Dai, R, Soderberg, C, Chen, L, Guerlavais, V, Horgan, K, Zhang, A, Sufi, B, Huang, H, Chen, H, Gangwar, S, Cardarelli, P, King, D. (2007). Efficacy study of anti-CD19 antibody drug-conjugates in Raji tumor xenograft and systemic model. Proc Amer Assoc Cancer Research 48, 4104.Google Scholar
Terrett, JA, Gangwar, S, Rao-Naik, C, Pan, C, Guerlavais, V, Huber, M, Chong, C, Green, L, Cardarelli, P, King, D, Deshpande, S, Rangan, V, Coccia, M, Lu, L, Passmore, D, Blansett, D, Dai, R, Sufi, B, Zhang, Q, Chen, L, Soderberg, C, Kwok, E, Horgan, K, Cortez, O, Sattari, P. (2007). Single, low dose treatment of lymphoma and renal cancer xenografts with human anti-CD70 antibody-toxin conjugates, results in long term cures. Proc Amer Assoc Cancer Res 48, 4112.Google Scholar
Hamann, PR, Hinman, LM, Beyer, CF, Lindh, D, Upeslacis, J, Shochat, D, Mountain, A (2005). A calicheamicin conjugate with a fully humanized anti-MUC1 antibody shows potent antitumor effects in breast and ovarian tumor xenografts. Bioconjug Chem 16, 354–360.CrossRefGoogle ScholarPubMed
Guillemard, V, Saragovi, H (2004). Prodrug chemotherapeutics bypass p-glycoprotein resistance and kill tumors in vivo with high efficacy and target-dependent selectivity. Oncogene 23, 3613–3621.CrossRefGoogle ScholarPubMed
Schrappe, M, Bumol, TF, Apelgren, LD, Briggs, SL, Koppel, GA, Markowitz, DD, Mueller, BM, Reisfeld, RA (1992). Long-term growth suppression of human glioma xenografts by chemoimmunoconjugates of 4-desacetylvinblastine-3-carboxyhydrazide and monoclonal antibody 9.2.27. Cancer Res 52, 3838–3844.Google ScholarPubMed
Mueller, BM, Wrasidlo, WA, Reisfeld, RA (1990). Antibody conjugates with morpholinodoxorubicin and acid-cleavable linkers. Bioconjug Chem 1, 325–330.CrossRefGoogle ScholarPubMed
Gillies, ER, Goodwin, A, Frechet, JM (2004). Acetals as pH-sensitive linkages for drug delivery. Bioconjug Chem 15, 1254–1263.CrossRefGoogle ScholarPubMed
Hamann, PR, Hinman, LM, Beyer, CF, Lindh, D, Upeslacis, J, Flowers, DA, Bernstein, I (2002). An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 13, 40–46.CrossRefGoogle ScholarPubMed
Hinman, LM, Hamann, PR, Wallace, R, Menendez, AT, Durr, FE, Upeslacis, J (1993). Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res 53, 3336–3342.Google ScholarPubMed
Thorpe, PE, Wallace, PM, Knowles, PP, Relf, MG., Brown, AN, Watson, GJ, Blakey, DC, Newell, DR (1988). Improved antitumor effects of immunotoxins prepared with deglycosylated ricin A-chain and hindered disulfide linkages. Cancer Res 48, 6396–6403.Google ScholarPubMed
Henry, MD, Wen, S, Silva, MD, Chandra, S, Milton, M, Worland, PJ (2004). A prostate-specific membrane antigen-targeted monoclonal antibody-chemotherapeutic conjugate designed for the treatment of prostate cancer. Cancer Res 64, 7995–8001.CrossRefGoogle ScholarPubMed
Tolcher, AW, Ochoa, L, Hammond, , Patnaik, A, Edwards, T, Takimoto, C, Smith, L, Bono, J, Schwartz, G, Mays, T, Jonak, ZL, Johnson, R, DeWitte, M, Martino, H, Audette, C, Maes, K, Chari, RV, Lambert, JM, Rowinsky, EK (2003). Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol 21, 211–222.CrossRefGoogle ScholarPubMed
Galsky, MD, Eisenberger, M, Moore-Cooper, S, Kelly, WK, Slovin, SF, DeLaCruz, A, Lee, Y, Webb, IJ, Scher, HI (2008). Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol 26, 2147–2154.CrossRefGoogle ScholarPubMed
Widdison, WC, Wilhelm, SD, Cavanagh, EE, Whiteman, KR, Leece, BA, Kovtun, Y, Goldmacher, VS, Xie, H, Steeves, RM, Lutz, RJ, Zhao, R, Wang, L, Blattler, WA, Chari, RV (2006). Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem 49, 4392–4408.CrossRefGoogle ScholarPubMed
Erickson, HK, Park, PU, Widdison, WC, Kovtun, YV, Garrett, LM, Hoffman, K, Lutz, RJ, Goldmacher, VS, Blattler, W (2006). Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 66, 4426–4433.CrossRefGoogle ScholarPubMed
Chen, Q, Millar, HJ, McCabe, FL, Manning, CD, Steeves, R, Lai, K, Kellogg, B, Lutz, RJ, Trikha, M, Nakada, MT, Anderson, GM (2007). Alphav integrin-targeted immunoconjugates regress established human tumors in xenograft models. Clin Cancer Res 13, 3689–3695.CrossRefGoogle ScholarPubMed
Dubowchik, GM, Firestone, RA (1998). Cathepsin B-sensitive dipeptide prodrugs. 1. A model study of structural requirements for efficient release of doxorubicin. Bioorg Med Chem Lett 8, 3341–3346.CrossRefGoogle ScholarPubMed
Dubowchik, GM, Mosure, K, Knipe, JO, Firestone, RA (1998). Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol), mitomycin C and doxorubicin. Bioorg Med Chem Lett 8, 3347–3352.CrossRefGoogle Scholar
Dubowchik, GM, Firestone, RA, Padilla, L, Willner, D, Hofstead, SJ, Mosure, K, Knipe, JO, Lasch, SJ, Trail, PA (2002). 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 13, 855–869.CrossRefGoogle ScholarPubMed
Walker, MA, Dubowchik, GM, Hofstead, SJ, Trail, PA, Firestone, RA (2002). Synthesis of an immunoconjugate of camptothecin. Bioorg Med Chem Lett 12, 217–219.CrossRefGoogle ScholarPubMed
Doronina, SO, Toki, BE, Torgov, MY, Mendelsohn, BA, Cerveny, CG, Chace, DF, DeBlanc, RL, Gearing, RP, Bovee, TD, Siegall, CB, Francisco, JA, Wahl, AF, Meyer, DL, Senter, PD (2003). Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21, 778–784.CrossRefGoogle ScholarPubMed
Sanderson, RJ, Hering, MA, James, SF, Sun, MM, Doronina, SO, Siadak, AW, Senter, PD, Wahl, AF (2005). In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res 11, 843–852.Google ScholarPubMed
Graaf, M, Boven, E, Scheeren, HW, Haisma, HJ, Pinedo, HM (2002). Beta-glucuronidase-mediated drug release. Curr Pharm Des 8, 1391–1403.CrossRefGoogle ScholarPubMed
Jeffrey, SC, Nguyen, MT, Moser, RF, Meyer, DL, Miyamoto, JB, Senter, PD (2007). Minor groove binder antibody conjugates employing a water soluble beta-glucuronide linker. Bioorg Med Chem Lett 17, 2278–2280.CrossRefGoogle ScholarPubMed
Alley, SC, Okeley, NM, Sanderson, RJ, Nanayakkara, V, Campbell, RL, Kline, TB, Doronina, SO, Jeffrey, SC, Benjamin, D, Senter, PD (2006). Intracellular metabolism of antibody-drug conjugates: identification and quantitation of released drugs. Proc Amer Assoc Cancer Res 47, 1992.Google Scholar
Boghaert, ER, Khandke, K, Sridharan, L, Armellino, D, Dougher, M, Dijoseph, JF, Kunz, A, Hamann, PR, Sridharan, A, Jones, S, Discafani, C, Damle, NK (2006). Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy. Int J Oncol 28, 675–684.Google ScholarPubMed
Hamblett, KJ, Senter, PD, Chace, DF, Sun, MM, Lenox, J, Cerveny, CG, Kissler, KM, Bernhardt, SX, Kopcha, AK, Zabinski, RF, Meyer, DL, Francisco, JA (2004). Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 10, 7063–7070.CrossRefGoogle ScholarPubMed
Chari, RV, Martell, BA, Gross, JL, Cook, SB, Shah, SA, Blattler, WA, McKenzie, SJ, Goldmacher, VS (1992). Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res 52, 127–131.Google ScholarPubMed
Packard, B, Edidin, M, Komoriya, A (1986). Site-directed labeling of a monoclonal antibody: targeting to a disulphide bond. Biochem. 25, 3548–3552.CrossRefGoogle Scholar
King, DJ, Turner, A, Farnsworth, APH, Adair, JR, Owens, RJ, Pedley, RB, Baldock, D, Proudfoot, KA, Lawson, ADG, Beeley, NRA, Millar, K, Millican, TA, Boyce, B, Antoniw, P, Mountain, A, Begent, RHJ, Shochat, D, Yarranton, GT (1994). Improved tumour targeting with chemically cross-linked recombinant antibody fragments. Cancer Res 54, 6176–6185.Google ScholarPubMed
Sun, MM, Beam, KS, Cerveny, CG, Hamblett, KJ, Blackmore, RS, Torgov, MY, Handley, FG, Ihle, NC, Senter, PD, Alley, SC (2005). Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides. Bioconjug Chem 16, 1282–1290.CrossRefGoogle ScholarPubMed
McDonagh, CF, Turcott, E, Westendorf, L, Webster, JB, Alley, SC, Kim, K, Andreyka, J, Stone, I, Hamblett, KJ, Francisco, JA, Carter, P (2006). Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Protein Eng Des Sel 19, 299–307.CrossRefGoogle ScholarPubMed
Lyons, A, King, DJ, Owens, RJ, Yarranton, GT, Millican, A, Whittle, NR, Adair, JR (1990). Site-specific attachment to recombinant antibodies via introduced surface cysteine residues. Protein Eng 3, 703–708.CrossRefGoogle ScholarPubMed
Stimmel, JB, Merrill, BM, Kuyper, LF, Moxham, CP, Hutchins, JT, Fling, ME, Kull, FC (2000). Site-specific conjugation on serine-cysteine variant monoclonal antibodies. J Biol Chem 275, 30445–30450.CrossRefGoogle Scholar
Junutula, JR, Bhakta, S, Raab, H, Ervin, KE, Eigenbrot, C, Vandlen, R, Scheller, RH, Lowman, HB (2008). Rapid identification of reactive cysteine residues for site-specific labeling of antibody-Fabs. J Immunol Methods 332, 41–52.CrossRefGoogle ScholarPubMed
Junutula, J, Raab, H, Bhakta, S, Parsons, K, Clark, S, Yu, S, Ross, S, Kim, A, McDorman, K, Flagella, K, Spencer, S, Vandlen, R, Lowman, HB, Mallet, W, Polakis, P, Sliwkowski, MX, Scheller, RH (2008). Site-specific conjugation of cytotoxic drugs to antibodies substantially improves the therapeutic window. Proc Amer Assoc Cancer Res 49, 2132.Google Scholar
Leung, S, Losman, MJ, Govidan, SV, Griffiths, GL, Goldenberg, DM, Hansen, HJ (1995). Engineering a unique glycosylation site for site-specific conjugation of haptens to antibody fragments. J Immunol 154, 5919–5926.Google ScholarPubMed
Hemminki, A, Hoffren, AM, Takkinen, K, Vehniainen, M, Makinen, ML, Pettersson, K, Teleman, O, Soderlund, H, Teeri, TT (1995). Introduction of lysine residues on the light chain constant domain improves the labelling properties of a recombinant Fab′ fragment. Protein Eng 8, 185–191.CrossRefGoogle Scholar
Stasi, R, Evangelista, ML, Buccisano, F, Venditti, A, Amadori, S (2008). Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer Treat Rev 34, 49–60.CrossRefGoogle ScholarPubMed
DiJoseph, JF, Armellino, DC, Boghaert, ER, Khandke, K, Dougher, MM, Sridharan, L, Kunz, A, Hamann, PR, Gorovits, B, Udata, C, Moran, JK, Popplewell, AG, Stephens, S, Frost, P, Damle, NK (2004). Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood 103, 1807–1814.CrossRefGoogle ScholarPubMed
Searcey, M (2002). Duocarmycins – natures prodrugs?Curr Pharm Des 8, 1375–1389.CrossRefGoogle ScholarPubMed
Boger, DL, Johnson, DS, Yun, W, Tarby, CM (1994). Molecular basis for sequence selective DNA alkylation by (+)- and ent-(-)-CC-1065 and related agents: alkylation site models that accommodate the offset AT-rich adenine N3 alkylation selectivity. Bioorg Med Chem 2, 115–135.CrossRefGoogle ScholarPubMed
Jeffrey, SC, Nguyen, MT, Andreyka, JB, Meyer, DL, Doronina, SO, Senter, PD (2006). Dipeptide-based highly potent doxorubicin antibody conjugates. Bioorg Med Chem Lett 16, 358–362.CrossRefGoogle ScholarPubMed
Ma, D, Hopf, CE, Malewicz, AD, Donovan, GP, Senter, PD, Goeckeler, WF, Maddon, PJ, Olson, WC (2006). Potent antitumor activity of an auristatin-conjugated fully human monoclonal antibody to prostate-specific membrane antigen. Clin Cancer Res 12, 2591–2596.CrossRefGoogle ScholarPubMed
Law, CL, Gordon, KA, Toki, BE, Yamane, AK, Hering, MA, Cerveny, CG, Petroziello, JM, Ryan, MC, Smith, L, Simon, R, Sauter, G, Oflazoglu, E, Doronina, SO, Meyer, DL, Francisco, JA, Carter, P, Senter, PD, Copland, JA, Wood, CG, Wahl, AF (2006). Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a potential therapeutic target for anti-CD70 antibody-drug conjugates. Cancer Res 66, 2328–2337.CrossRefGoogle ScholarPubMed
Rodon, J, Garrison, M, Hammond, , Bono, J, Smith, L, Forero, L, Hao, D, Takimoto, C, Lambert, JM, Pandite, L, Howard, M, Xie, H, Tolcher, AW (2008). Cantuzumab mertansine in a three-times a week schedule: a phase I and pharmacokinetic study. Cancer Chemother Pharmacol 62, 911–919.CrossRefGoogle Scholar
Qin, A, Watermill, RA, Mastico, RA, Lutz, RJ, O'Keefe, J, Zildjian, S, Mita, AC, Phan, AT, Tolcher, AW (2008). The pharmacokinetics and pharmacodynamics of IMGN242 (huC242-DM4) in patients with CanAg-expressing solid tumors. J Clin Oncol 26, May 20 suppl., 3066.CrossRefGoogle Scholar
Leipold, DD, Jumbe, N, Dugger, D, Crocker, L, Leach, W, Sliwkowski, MX, Meyer, D, Senter, PD, Tibbitts, J (2007). Trastuzumab-MC-vc-PAB-MMAF: The effects of the Drug:Antibody Ratio (DAR) on efficacy, toxicity and pharmacokinetics. Proc Amer Assoc Cancer Res 48, 1551.Google Scholar
Younes, A, Forero-Torres, A, Bartlett, NL, Leonard, JP, Rege, B, Kennedy, DA, Lorenz, JM, Sievers, EL (2008). Objective responses in a phase I dose escalation study of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in patients with relapsed or refractory Hodgkin lymphoma. J Clin Oncol 26, May 20 suppl., 8526.CrossRefGoogle Scholar
Hwu, P, Sznol, M, Kluger, H, Rink, L, Kim, KB, Papadopoulos, NE, Sanders, D, Boasberg, P, Ooi, CE, Hamid, O (2008). A phase I/II study of CR011-vcMMAE an antibody toxin conjugate drug in patients with unresectable stage III/IV melanoma. J Clin Oncol 26, May 20 suppl. 9029.CrossRefGoogle Scholar

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