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Engineering Antibodies for Cancer Therapy

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Antibody Expression and Production

Part of the book series: Cell Engineering ((CEEN,volume 7))

Abstract

Over the past 20 years monoclonal antibodies (mAbs) have evolved to become a major class of therapeutics for the treatment of a variety of indications, including cancer. The evolution of mAbs into front-line cancer therapies required significant advances in the strategies used to both isolate and optimize these agents. Here we discuss development of the steps that facilitated this evolution and the criteria that drive current development of next-generation mAb-based cancer therapies.

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References

  • Abes, R. & Teillaud, J. (2010) Imapct of glycosylation on effector functions of therapeutic IgG. Pharmaceuticals, 3, 146–157.

    CAS  Google Scholar 

  • Abhinandan, K. R. & Martin, A. C. R. (2007) Analyzing the “degree of humanness” of antibody seqences. Journal of Molecular Biology, 369, 852–862.

    PubMed  CAS  Google Scholar 

  • Adams, G. P., Schier, R., Mccall, A. M., Simmons, H. H., Horak, E. M., Alpaugh, R. K., Marks, J. D. & Weiner, L. M. (2001) High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Research, 61, 4750–4755.

    PubMed  CAS  Google Scholar 

  • Albrecht, H. (2010) Role of antibodies in cancer treatment (an overview). In Hayat, M. A. (Ed.) Methods of Cancer Diagnosis, Therapy, and Prognosis. Houten, Netherlands, Springer.

    Google Scholar 

  • Almagro, J. C. & Fransson, J. (2008) Humanization of antibodies. Frontiers in Bioscience, 13, 1619–1633.

    PubMed  CAS  Google Scholar 

  • Alonso-Camino, V., Sanchez-Martin, D., Compte, M., Sanz, L. & Alvarez-Vallina, L. (2009) Lymphocyte display: A novel antibody selection platform based on T cell activation. Public Library of Science, 4, e7174.

    Google Scholar 

  • Alt, F. W., Blackwell, T. K. & Yancopoulos, G. D. (1985) Immunoglobulin genes in transgenic mice. Trends in Genetics, 1, 231–236.

    Google Scholar 

  • Azinovic, I., Denardo, G. L., Lamborn, K. R., Mirick, G., Goldstein, D., Bradt, B. M. & Denardo, S. J. (2006) Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies. Cancer Immunology and Immunotherapy, 55, 1451–1458.

    PubMed  CAS  Google Scholar 

  • Baca, M., Presta, L. G., O’Connor, S. J. & Wells, J. A. (1997) Antibody humanization using phage display. Journal of Biological Chemistry, 272, 10678–10684.

    PubMed  CAS  Google Scholar 

  • Badger, C. C., Anasetti, C., Davis, J. & Bernstein, I. D. (1987) Treatment of malignancy with unmodified antibody. Pathology and Immunopathology Research, 6, 419–434.

    PubMed  CAS  Google Scholar 

  • Baeuerle, P. A. & Reinhardt, C. (2009) Bispecific T-cell engaging antibodies for cancer therapy. Cancer Research, 69, 4941–4944.

    PubMed  CAS  Google Scholar 

  • Bagga, S., Seth, D. & Batra, J. K. (2002) The cytotoxic activity of ribosome-inactivating protein saporin-6 is attributed to its rRNA N-glycosidase and internucloesomal DNA fragmentation activities. Journal of Biological Chemistry, 287, 4813–4820.

    Google Scholar 

  • Baluna, R. & Vitetta, E. S. (1997) Vascular leak syndrome: A side effect of immunotherapy. Immunopharmacology, 37, 117–132.

    PubMed  CAS  Google Scholar 

  • Barbas, C. F. & Lerner, R. A. (1991) Combinatorial immunoglobulin libraries on the surface of phage (Phabs): Rapid selection of antigen-specific fabs. Methods, 2, 119–124.

    CAS  Google Scholar 

  • Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., Einsele, H., Brandl, C., Wolf, A., Kirchinger, P., Klappers, P., Schmidt, M., Riethmuller, G., Reinhardt, C., Baeuerle, P. A. & Kufer, P. (2008) Tumor regression in cancer patients by very low doses or a T cell-engaging antibody. Science, 321, 974–977.

    PubMed  CAS  Google Scholar 

  • Baselga, J., Gelmon, K. A., Verma, S., Wardley, A., Conte, P., Miles, D., Bianchi, G., Cortes, J., Mcnally, V. A., Ross, G. A., Fumoleau, P. & Gianni, L. (2010) Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2 – Positive metastatic breast cancer that progressed during prior trastuzumab therapy. Journal of Clinical Oncology, 28, 1138–1144.

    PubMed  CAS  Google Scholar 

  • Beck, A. K., Pass, H. I., Carbone, M. & Yang, H. (2008b) Ranpirnase as a potential antitumor ribonuclease treatment for mesothelioma and other malignancies. Future Oncology, 4, 341–349.

    PubMed  CAS  Google Scholar 

  • Beck, A., Wagner-Rousset, E., Bussat, M., Lokteff, M., Klinguer-Hamour, C., Haeuw, J., Goetsch, L., Wurch, T., Can Dorsselaer, A. & Corvaia, N. (2008a) Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins. Current Pharmaceutical Biotechnology, 9, 482–501.

    PubMed  CAS  Google Scholar 

  • Bernett, M. J., Karki, S., Moore, G. L., Leung, I. W. L., Chen, H., Pong, E., Nguyen, D. T., Jacinto, J., Zalevsky, J., Muchhal, U. S., Desjarlais, J. R. & Lazar, G. A. (2010) Engineering fully human monoclonal antibodies from murine variable regions. Journal of Molecular Biology, 396, 1474–1490.

    PubMed  CAS  Google Scholar 

  • Blum, K. A., Smith, M., Fung, H., Zalevsky, J., Combs, D., Ramies, D. A. & Younes, A. (2009) Phase I study of an anti-CD30 Fc engineered humanized monoclonal antibody in Hodgkin lymphoma (G+HL) or anaplastic large cell lymphoma (ALCL) patients: Safety, pharmacokinetics (PK), immunogenicity, and efficacy. 2009 ASCO Annual Meeting. Abstract #8531, Orlando, FL.

    Google Scholar 

  • Boder, E. T. & Wittrup, K. D. (1997) Yeast surface display for screening combinatorial polypeptide libraries. Nature Biotechnology, 15, 553–557.

    PubMed  CAS  Google Scholar 

  • Boder, E. T. & Wittrup, K. D. (2000) Yeast surface display for directed evolution of protein expression, affinity, and stability. Methods in Enzymology, 328, 430–444.

    PubMed  CAS  Google Scholar 

  • Boerner, P., Lafond, R., Lu, W., Brams, P. & Royston, I. (1991) Production of antigen-specific human monoclonal antibodies from in vitro-primed human splenocytes. Journal of Immunology, 147, 86–95.

    CAS  Google Scholar 

  • Borrebaeck, C. A. K., Danielsson, L. & Moller, S. A. (1988) Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proceedings of the National Academy of Sciences of the USA, 85, 3995–3999.

    PubMed  CAS  Google Scholar 

  • Boulianne, G. L., Hozumi, N. & Shulman, M. J. (1984) Production of functional chimaeric mouse/human antibody. Nature, 312, 643–646.

    PubMed  CAS  Google Scholar 

  • Bourne, P. C., Terzyan, S. S., Cloud, G., Landolfi, N. F., Casquez, M. & Edmundson, A. B. (2004) Three-dimensional structures of a humanized anti-IFN-gamma Fab (HuZAF) in two crystal structures. Acta Crystallographica, D60, 1761–1769.

    CAS  Google Scholar 

  • Bradbury, A. R. M. & Marks, J. D. (2004) Antibodies from phage antibody libraries. Journal of Immunological Methods, 290, 29–49.

    PubMed  CAS  Google Scholar 

  • Brischwein, K., Schlereth, B., Guller, B., Steiger, C., Wolf, A., Lutterbuese, R., Offner, S., Locher, M., Urbig, T., Raum, T., Kleindienst, P., Wimberger, P., Kimmig, R., Fichtner, I., Kufer, P., Hofmeister, R., Da Silva, A. J. & Baeuerle, P. A. (2006) MT110: A novel bispecific single-chain antibody construct with high efficacy in eradicating established tumores. Molecular Immunology, 43, 1129–1143.

    PubMed  CAS  Google Scholar 

  • Brooks, S. A. (2004) Appropriate glycosylation of recombinant proteins for human use. Molecular Biotechnology, 23, 241–255.

    Google Scholar 

  • Bruggemann, M., Caskey, H. M., Teale, C., Waldmann, H., Williams, G. T., Surani, M. A. & Neuberger, M. S. (1989) A repertoire of monoclonal antibodies with human heavy chains from transgenic mice. Proceedings of the National Academy of Sciences of the USA, 86, 6709–6713.

    PubMed  CAS  Google Scholar 

  • Bruggemann, M., Willimas, G. T., Bindon, C. I., Clark, M. R., Walker, M. R., Jefferis, R., Waldmann, H. & Neuberger, M. S. (1987) Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. Journal of Experimental Medicine, 166, 1351–1361.

    PubMed  CAS  Google Scholar 

  • Byrne, B., Donohoe, G. G. & O’Kennedy, R. (2007) Sialic acids: Carbohydrate moieties that influence the biological and physical properties of biopharmaceutical proteins and living cells. Drug Discovery Today, 12, 319–326.

    PubMed  CAS  Google Scholar 

  • Carter, P. (2001) Bispecific human IgG by design. Journal of Immunological Methods, 248, 7–15.

    PubMed  CAS  Google Scholar 

  • Carter, P. J. (2006) Potent antibody therapeutics by design. Nature Reviews Immunology, 6, 343–357.

    PubMed  CAS  Google Scholar 

  • Carter, P., Presta, L., Gorman, C. M., Ridgway, J. B., Henner, D., Wong, W. L., Rowland, A. M., Kotts, C., Carver, M. E. & Shepard, H. M. (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proceedings of the National Academic of Sciences of the USA, 89, 4285–4289.

    CAS  Google Scholar 

  • Carter, P. J. & Senter, P. D. (2008) Antibody-drug conjugates for cancer therapy. Cancer Journal, 14, 154–169.

    CAS  Google Scholar 

  • Chang, C., Gupta, P., Michel, R., Loo, M., Wang, Y., Cardillo, T. M. & Gondenberg, D. M. (2010) Ranpirnase (frog RNase) targeted with a humanized internalizing, anti-Trop-2 antibody has potent cytotoxicity against diverse epithelial cancer cells. Molecular Cancer Therapeutics, 9, 2276–2286.

    PubMed  CAS  Google Scholar 

  • Chaudhury, C., Brooks, C. L., Carter, D. C., Robinson, J. M. & Anderson, C. L. (2006) Albumin binding to FcRn: Distinct from the FcRn-IgG interaction. Biochemistry, 45, 4983–4990.

    PubMed  CAS  Google Scholar 

  • Chaudhury, C., Mehnaz, S., Robinson, J. M., Hayton, W. L., Pearl, D. K., Roopenian, D. C. & Anderson, C. L. (2003) The major histocompatibilty complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. Journal of Experimental Medicine, 197, 315–322.

    PubMed  CAS  Google Scholar 

  • Chothia, C. & Lesk, A. M. (1987) Canonical structures for the hypervariable regions of immunoglobulins. Journal of Molecular Biology, 196, 901–917.

    PubMed  CAS  Google Scholar 

  • Co, M. S., Avdalovic, N. M., Caron, P. C., Avdalovic, M. V., Scheinberg, D. A. & Queen, C. (1992) Chimeric and humanized antibodies with specificity for the CD33 antigen. Journal of Immunology, 148, 1149–1154.

    CAS  Google Scholar 

  • Colby, D. W., Kellogg, B. A., Graff, C. P., Yeung, Y. A., Swers, J. S. & Wittrup, K. D. (2004) Engineering antibody affinity by yeast surface display. Methods in Enzymology, 388, 348–358.

    PubMed  CAS  Google Scholar 

  • Cole, S. P., Campling, B. G., Louwman, I. H., Kozbor, D. & Roder, J. C. (1984) A strategy for the production of human monoclonal antibdies reactive with lung tumor cell lines. Cancer Research, 44, 2750–2753.

    PubMed  CAS  Google Scholar 

  • Constantinou, A., Chen, C. & Doeonarain, M. P. (2010) Modulating the pharmacokinetics of therapeutic antibodies. Biotechnology Letters, 32, 609–622.

    PubMed  CAS  Google Scholar 

  • Currie, G. A. (1972) Eighty years of immunotherapy: A review of immunological methods used for the treatment of human cancer. British Journal of Cancer, 26, 141–153.

    PubMed  CAS  Google Scholar 

  • Dall’Acqua, W. F., Kiener, P. A. & Wu, H. (2006) Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). Journal of Biological Chemistry, 281, 23514–23524.

    PubMed  Google Scholar 

  • Denlinger, C. S., Beeram, M., Tolcher, A. W., Goldstein, L. J., Slichenmyer, W. J., Murray, J., Mcdonagh, C. F., Andreas, K. & Moyo, V. M. (2010) A phase I/II and pharmacologic study of MM-111 in patients with advanced, refractory HER2-positive (HER2+) cancers. Journal of Clinical Oncology, 28, TPS169.

    Google Scholar 

  • Dennis, M. S., Jin, H., Dugger, D., Yang, R., Mcfarland, L., Ogasawara, A., Williams, S., Cole, M. J., Ross, S. & Schwall, R. (2007) Imging tumors with an albumin-binding Fab, a novel tumor-targeting agent. Cancer Research, 67, 254–261.

    PubMed  CAS  Google Scholar 

  • Dennis, M. S., Zhang, M., Meng, Y. G., Kadkhodayan, M., Kirchhofer, D., Combs, D. & Damico, L. A. (2002) Albumin binding as a general strategy for improving the pharmacokinetics of proteins. Journal of Biological Chemistry, 277, 35035–35043.

    PubMed  CAS  Google Scholar 

  • Desjarlais, J. R. (2005) Protein engineering with analogous contact environments. In Wipo (Ed.) WO/2005/057486. G06F 19/00 (2006.01) ed. USA.

    Google Scholar 

  • Desmet, J., Vanhoorelbeke, K. & Deckmyn, H. (2010) Humanization by resurfacing. In Kontermann, R. & Dubel, S. (Eds.) Antibody Engineering, 2nd ed. Heidelberg, Springer.

    Google Scholar 

  • Elliott, S., Lorenzini, T., Asher, S., Aoki, K., Brankow, D., Buck, L., Busse, L., Chang, D., Fuller, J., Grant, J., Hernday, N., Hokum, M., Hu, S., Knudten, A., Levin, N., Komorowski, R., Martin, F., Navarro, R., Osslund, T., Rogers, G., Rogers, N., Trail, G. & Egrie, J. (2003) Enhancement of therapeutic protein in vivo activities through glycoengineering. Nature Biotechnology, 21, 414–421.

    PubMed  CAS  Google Scholar 

  • Erickson, H. K., Park, P. U., Widdison, W. C., Kovtun, Y. V., Garrett, L. M., Hoffman, K., Lutz, R. J., Goldmacher, V. S. & Blattler, W. A. (2006) Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Research, 66, 4426–4433.

    PubMed  CAS  Google Scholar 

  • Feldhaus, J. M., Siegel, R. W. & Wittrup, K. D. (2003) Yeast Display scFv Antibody Library User’s Manual. Richland, WA, Pacific Northwest National Laboratory.

    Google Scholar 

  • Fiedler, W. M., Ritter, B., Seggewiss, R., Bokemeyer, C., Fettes, P., Klinger, M., Vieser, E., Reuttinger, D., Kaubitzsch, S. & Wolf, M. (2010) Phase I safety and pharmacology study of the EPCAM/CD3-bispecific antibody MT110 in patients with metastatic colorectal, gastric, or lung cancer. Journal of Clinical Oncology, 28, 2573.

    Google Scholar 

  • Foote, J. & Winter, G. (1992) Antibody framework residues affecting the conformation of the hypervariable loops. Journal of Molecular Biology, 224, 487–499.

    PubMed  CAS  Google Scholar 

  • Fujimori, K., Covell, D. G., Fletcher, J. E. & Weinstein, J. N. (1990) A modeling analysis of monoclonal antibody percolation through tumors: A binding site barrier. The Journal of Nuclear Medicine, 31, 1191–1198.

    CAS  Google Scholar 

  • Gennari, R., Menard, S., Fagnoni, F., Ponchio, L., Scelsi, M., Tagliabue, E., Castiglioni, F., Villani, L., Magalotti, C., Gibelli, N., Oliviero, B., Ballardini, B., Da Prada, G., Zambelli, A., & Costa, A. (2004) Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clinical Cancer Research, 10, 5650–5655.

    PubMed  CAS  Google Scholar 

  • Ghetie, V., Popov, S., Borvak, J., Radu, C., Matesoi, D., Medesan, C., Ober, R. J. & Ward, E. S. (1997) Increasing the serum persistence of an IgG fragment by random mutagenesis. National Biotechnology, 15, 637–640.

    CAS  Google Scholar 

  • Ghetie, V. & Ward, E. S. (2000) Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annual Review of Immunology, 18, 739–766.

    PubMed  CAS  Google Scholar 

  • Giusti, R. M., Shastri, K. A., Cohen, M. H., Keegan, P. & Pazdur, R. (2007) FDA approval summary: Panitumumab (Vectibix). Oncologist, 12, 577–583.

    PubMed  CAS  Google Scholar 

  • Glassy, M. C. & Ferrone, S. (1982) Differential segregation patters of human chromosomes in somatic cell hybrids constructed with human B-lymphocytes and human melanoma cells. Cancer Research, 42, 3971–3973.

    PubMed  CAS  Google Scholar 

  • Gonzales, N. R., Padlan, E. A., De Pascalis, R., Schuck, P., Schlom, J. & Kashmiri, S. V. S. (2004) SDR grafting of a murine antibody using multiple human germline templates to minimize its immunogenicity. Molecular Immunology, 40, 863–872.

    Google Scholar 

  • Gorman, S. D., Clark, M. R., Routledge, E. G., Cobbold, S. P. & Waldmann, H. (1991) Reshaping a therapeutic CD4 antibody. Proceedings of the National Academic of Sciences of the USA, 88, 4181–4185.

    CAS  Google Scholar 

  • Govindan, S. V. & Goldenberg, D. M. (2010) Immunoconjugate anticancer therapeutics. In Reddy, L. H. & Couvreur, P. (Eds.) Macromolecular Anticancer Therapeutics. New York, NY, Springer.

    Google Scholar 

  • Graziano, R. F., Tempest, P. R., White, P., Keler, T., Deo, Y., Ghebremariam, H., Coleman, K., Pfefferkorn, L. C., Fanger, M. W. & Guyre, P. M. (1995) Construction and characterization of a humanized anit-gamma-Ig receptor type I monoclonal antibody. Journal of Immunology, 155, 4996–5002.

    CAS  Google Scholar 

  • Green, L. L., Hardy, M. C., Maynard-Currie, C. E., Tsuda, H., Louie, D. M., Mendez, M. J., Abderrahim, H., Noguchi, M., Smith, D. H., Zeng, Y., David, N. E., Sasai, H., Garza, D., Brenner, D. G., Hales, J. F., Mcguinness, R. P., Capon, D. J., Klapholz, S. & Jakobovits, A. (1994) Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nature Genetics, 7, 13–21.

    PubMed  CAS  Google Scholar 

  • Haas, C., Krinner, E., Brischwein, K., Hoffmann, P., Lutterbuse, R., Schlereth, B., Kufer, P. & Baeuerle, P. A. (2009) Mode of cytotoxic action of T-cell engaging BiTE antibody MT110. Immunobiology, 214, 441–453.

    PubMed  CAS  Google Scholar 

  • Hamilton, S. R., Bobrowicz, P., Bobrowicz, B., Davidson, R. C., Li, H., Mitchell, T., Nett, J. H., Rausch, S., Stadheim, T. A., Wischnewski, H., Wildt, S. & Gerngross, T. U. (2003) Production of complex human glycoproteins in yeast. Science, 301, 1244–1246.

    PubMed  CAS  Google Scholar 

  • Hanes, J., Jermutus, L., Weber-Bornhauser, S., Bosshard, H. R. & Pluckthun, A. (1998) Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proceedings of the National Academy of Sciences of the USA, 95, 14130–14135.

    PubMed  CAS  Google Scholar 

  • Harris, J. M. & Chess, R. B. (2003) Effect of pegylation on pharmaceuticals. Nature Reviews Drug Discovery, 214, 214–221.

    Google Scholar 

  • Hecht, J. R., Patnaik, A., Berlin, J., Venook, A., Malik, I., Tchekmedyian, S., Navale, L., Amado, R. G. & Meropol, N. J. (2007) Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer, 10, 980–988.

    Google Scholar 

  • Hericourt, J. & Richet, C. (1895) Traitement d’un cas de sarcome par la serotherapie. Comptes Rendus Hebdomadaires des Seances de l Academie des Sciences, 120, 948–950.

    Google Scholar 

  • Hinton, P. R., Johlfs, M. G., Xiong, J. M., Hanestad, K., Ong, K. C., Bullock, C., Keller, S., Tang, M. T., Tso, J. Y., Vasquez, M. & Tsurushita, N. (2004) Engineered human IgG antibodies with longer serum half-lives in primates. Journal of Biological Chemistry, 279, 6213–6216.

    PubMed  CAS  Google Scholar 

  • Hinton, P. R., Xiong, J. M., Johlfs, M. G., Tang, M. T., Keller, S. & Tsurushita, N. (2006) An engineered human IgG1 anitbody with longer serum half-life. Journal of Immunology, 176, 346–356.

    CAS  Google Scholar 

  • Holt, L. J., Basran, A., Jones, K., Chorlton, J., Jespers, L. S., Brewis, N. D. & Tomlinson, I. M. (2008) Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. Protein Engineering, Design & Selection, 21, 283–288.

    CAS  Google Scholar 

  • Hoogenboom, H. R., Griffiths, A. D., Johnson, K. S., Chiswell, D. J., Hudson, P. J. & Winter, G. (1991) Multi-subunit proteins on the surface of filamentous phage: Methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Research, 19, 4133–4137.

    PubMed  CAS  Google Scholar 

  • Hopp, J., Hornig, N., Zettlitz, K. A., Schwarz, A., Fu, N., Muller, D. & Kontermann, R. E. (2010) The effects of affinity and valency of an albumin-binding domain (ABD) on the half-life of a single-chain diabody-ABD fusion protein. Protein Engienering, Design & Selection, 23, 827–834.

    Google Scholar 

  • Horton, H. M., Bernett, M. J., Pong, E., Peipp, M., Karki, S., Chu, S. Y., Richards, J. O., Vostiar, I., Joyce, P. F., Repp, R., Desjarlais, J. R. & Zhukovsky, E. A. (2008) Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Research, 68, 8049–8057.

    PubMed  CAS  Google Scholar 

  • Houghton, A. N., Brooks, H., Cote, R. J., Taormina, M. C., Oettgen, H. F. & Old, L. J. (1983) Detection of cell surface and intracellular antigens by human monoclonal antibodies: Hybrid cell lines derived from lymphocytes of patients with malignant melonoma. Journal of Experimental Medicine, 158, 53–65.

    PubMed  CAS  Google Scholar 

  • Huhalov, A., Adams, S., Paragas, V., Oyama, S., Overland, R., Luus, L., Gibbons, F., Zhang, B., Nguyen, S., Nielsen, U. B., Niyikiza, C., Mcdonagh, C. F. & Kudla, A. J. (2010) MM-111, an ErbB2/ErbB3 bispecific antibody with potent activity in ErbB2-overexpressing cells, positively combines with trastuzumab to inhibit growth of breast cancer cells driven by the ErbB2/ErbB3 oncogenic unit. Proceedings of the AACR, Washington DC, Abstract 3485.

    Google Scholar 

  • Huse, W. D., Sastry, L., Iverson, S. A., Kang, A. S., Alting-Mees, M., Burton, D. R., Benkovic, S. J. & Lerner, R. A. (1989) Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science, 246, 1275–1281.

    PubMed  CAS  Google Scholar 

  • Hwang, W. Y. K. & Foote, J. (2005) Immunogenicity of engineered antibodies. Methods, 36, 3–10.

    PubMed  CAS  Google Scholar 

  • Idusogie, E. E., Wong, P. Y., Presta, L. G., Gazzano-Santoro, H., Totpal, K., Ultsch, M. & Mulkerrin, M. G. (2001) Engineered antibodies with increased activity to recruit complement. Journal of Immunology, 166, 2571–2575.

    CAS  Google Scholar 

  • Imai-Nishiya, H., Mori, K., Inoeu, M., Wakitani, M., Iida, S., Shitara, K. & Satoh, M. (2007) Double knockdown of alpha1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6-dehytratase (GMD) in antibody-producing cells: A new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC. BMC Biotechnology, 7:84.doi:10.1186/1472-6750-7-84.

    Google Scholar 

  • Jacobs, P. P., Geysens, S., Vervecken, W., Contreras, R. & Callewaert, N. (2009) Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology. Nature Protocols, 4, 58–70.

    PubMed  CAS  Google Scholar 

  • Jain, R. K. (1987) Transport of molecules in the tumor interstitum: A review. Cancer Research, 47, 3039–3051.

    PubMed  CAS  Google Scholar 

  • Jain, R. K. (1990) Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Research, 50, 814–819.

    Google Scholar 

  • Jones, P. T., Dear, P. H., Foote, J., Nueuberger, M. S. & Winter, G. (1986) Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature, 321, 522–525.

    PubMed  CAS  Google Scholar 

  • Junghans, R. P. & Anderson, C. L. (1996) The protection receptor for IgG catabolism is the B2-microglobulin-containing neonatal intestinal transport receptor. Proceedings of the National Academy of Sciences of the USA, 93, 5512–5516.

    PubMed  CAS  Google Scholar 

  • Kabat, E. A. (1978) The structural basis for antibody complementary. Advances in Protein Chemistry, 32, 1–75.

    PubMed  CAS  Google Scholar 

  • Kanda, Y., Yamada, T., Mori, K., Okazaki, A., Inoeu, M., Kitajima-Miyama, K., Kuni-Kamochi, R., Nakano, R., Yano, K., Kakita, S., Shitara, K. & Satoh, M. (2006a) Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three differnt N-linked Fc oligosaccharides: The high-mannose, hybrid, and complex types. Glycobiology, 17, 104–118.

    PubMed  Google Scholar 

  • Kanda, Y., Yamane-Ohnuki, N., Sakai, N., Yamano, K., Nakano, R., Inoeu, M., Misaka, H., Iida, S., Wakitani, M., Konno, Y., Yano, K., Shitara, K., Hosoi, S. & Satoh, M. (2006b) Comparison of cell lines for stable production of fucose-negative antibodies with enhanced ADCC. Biotechnology and Bioengineering, 94, 680–688.

    PubMed  CAS  Google Scholar 

  • Karpas, A., Dremucheva, A. & Czepulkowski, B. H. (2001) A human myeloma cell line suitable for the generation of human monoclonal antibodies. Proceedings of the National Academy of Sciences of the USA, 98, 1799–1804.

    PubMed  CAS  Google Scholar 

  • Keler, T., Graziano, R. F., Mandal, A., Wallace, P. K., Fisher, J., Guyre, P. M., Fanger, M. W. & Deo, Y. M. (1997) Bispecific antibody-dependent cellular cytotoxicity of HER2/new-overexpressing tumor cells by FCgamma receptor type I-expressing effector cells. Cancer Research, 57, 4008–4014.

    PubMed  CAS  Google Scholar 

  • Kempeni, J. (1999) Preliminary results of early clinical trials with the fully human anti-TNFalpha monoclonal antibody D2E7. Annals of the Rheumatic Diseases, 58(Suppl I), I70–I72.

    PubMed  CAS  Google Scholar 

  • Kenanova, V., Olafsen, T., Crow, D. M., Sundaresan, G., Subbarayan, M., Carter, N. H., Ikle, D. N., Yazaki, P. J., Chatziioannou, A. F., Gambhir, S. S., Williams, L. E., Shively, J. E., Colcher, D., Raubitschek, A. A. & Wu, A. M. (2005) Tailoring the pharmacokinetics and positron emission tomography imaging properties of anti-carcinoembryonic antigen single-chain Fv-Fc antibody fragments. Cancer Research, 65, 622–631.

    PubMed  CAS  Google Scholar 

  • Khazaeli, M. B., Conry, R. M. & Lobuglio, A. F. (1994) Human immune-response to monoclonal-antibodies. Journal of Immunotherapy, 15, 42–52.

    PubMed  CAS  Google Scholar 

  • Kim, S. J., Park, I. & Hong, H. J. (2010) Human antibodies by guided selection. In Kontermann, R. & Dubel, S. (Eds.) Antibody Engineering, 2nd ed. Heidelberg, Springer.

    Google Scholar 

  • Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., Hoess, A., Wolle, J., Pluckthun, A. & Virnekas, B. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consenses frameworks and CDRs randomized with trinucleotides. Journal of Molecular Biology, 296, 57–86.

    PubMed  CAS  Google Scholar 

  • Knight, D. M., Wagner, C., Jordan, R., Mcaleer, M. F., Derita, R., Fass, D. N., Coller, B. S., Weisman, H. F. & Ghrayeb, J. (1995) The immunogenicity of the 7E3 murine monoclonal Fab antibody fragment variable region is dramatically reduced in humans by substitution of human for murine constant regions. Molecular Immunology, 32, 1271–1281.

    PubMed  CAS  Google Scholar 

  • Kohler, G. & Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256, 495–497.

    PubMed  CAS  Google Scholar 

  • Komissarov, A. A., Calcutt, M. J., Marchbank, M. T., Peletskaya, E. N. & Deutsher, S. L. (1996) Equilibrium binding studies of recombinant anti-single-stranded DNA Fab. Role of heavy chain complementarity-determining regions. Journal Biological Chemistry, 271, 12241–12246.

    CAS  Google Scholar 

  • Kornfeld, R. & Kornfeld, S. (1985) Assembly of asparagine-linked oligosaccharides. Annual Review of Biochemistry, 54, 631–664.

    PubMed  CAS  Google Scholar 

  • Kozbor, D. & Roder, J. C. (1981) Requirements for the establishment of high-titered human monoclonal antibodies against tetanus toxoid using the epstein-barr virus technique. Journal of Immunology, 127, 1275–1280.

    CAS  Google Scholar 

  • Kreitman, R. J. (2006) Immunotoxins for targeted cancer therapy. The AAPS Journal, 8, E532–E551.

    PubMed  CAS  Google Scholar 

  • Kricka, L. J. (1999) Human anti-animal antibody interferences in immunological assays. Clinical Chemistry, 45, 942–956.

    PubMed  CAS  Google Scholar 

  • Krop, I., Lorusso, P., Miller, K. D., Modi, S., Yardley, D., Rodriguez, G., Agresta, S., Zheng, M., Amler, L. & Rugo, H. (2009) A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody-drug conjugate, in patients with HER2+ metastatic breast cancer who were previously treated with an anthracyline, a taxane, capecitabine, lapatinib, and trastuzumab. San Antonio Breast Cancer Symposium, San Antonio, TX.

    Google Scholar 

  • Kubetzko, S., Balic, E., Wiaibel, R., Zangemeister-Wittke, U. & Pluckthun, A. (2006) PEGylation and multimerization of the anti-p185 HER-2 single chain Fv fragment 4D5. Journal of Biological Chemistry, 281, 35186–35201.

    PubMed  CAS  Google Scholar 

  • Kudo, T., Asao, A. & Tachibana, T. (1988) Highly efficient procedure for production of human monoclonal antibodies: Establishment of hybrids between Epstein-Barr virus-transformed B lymphocytes and hetermyeloma cells by use of GIT culture medium. Tohoku Journal of Experimental Medicine, 154, 345–355.

    PubMed  CAS  Google Scholar 

  • Lazar, G. A., Dang, W., Karki, S., Vafa, O., Peng, J. S., Hyun, L., Chan, C., Chung, H. S., Eivazi, A., Yoder, S. C., Vielmetter, J., Carmichael, D. F., Hayes, R. J. & Dahiyat, B. I. (2006) Engineered antibody Fc variants with enhanced effector funciton. Proceedings of the National Academy of Sciences of the USA, 103, 4005–4010.

    PubMed  CAS  Google Scholar 

  • Lazar, G. L., Desjarlais, J. R., Jacinto, J., Karki, S. & Hammond, P. W. (2007) A molecular immunology approach to antibody humanization and functional optimization. Molecular Immunology, 44, 1986–1998.

    PubMed  CAS  Google Scholar 

  • Lee, J. E. & Raines, R. T. (2008) Ribonucleases as novel chemotherapeutics: The ranpirnase example. BioDrugs, 22, 53–58.

    PubMed  CAS  Google Scholar 

  • Lefranc, M., Giudicelli, V., Kaas, Q., Duprat, E., Jabado-Michaloud, J., Scaviner, D., Ginestoux, C., Clement, O., Chaume, D. & Lefranc, G. (2005) IGMT, the international ImMunoGeneTics information system. Nucleic Acids Research, 33, D593–D597.

    PubMed  CAS  Google Scholar 

  • 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., Wong, W. L., Jacobson, F. S., Koeppen, H., Schwall, R. H., Kenkare-Mitra, S. R., Spencer, S. D. & Sliwkowski, M. X. (2008) Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Research, 68, 9280–9290.

    PubMed  CAS  Google Scholar 

  • Li, J., Sai, T., Berger, M., Chao, W., Davidson, D., Deshmukh, G., Drozdowski, B, Ebel, W., Harley, S., Henry, M., Jacob, S., Yao, J., Zhou, Y., Kavuru, M., Bonfield, T., Thomassen, M. J., Sass, P. M., Nicolaides, N. C. & Grasso, L. (2006b) Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proceedings of the National Academy of Sciences of the USA, 103, 3557–3562.

    PubMed  CAS  Google Scholar 

  • Li, H., Sethuraman, N., Stadheim, T. A., Zha, D., Prinz, B., Ballew, N., Bobrowicz, P., Choi, B., Cook, W. J., Cukan, M., Houston-Cummings, N. R., Davidson, R., Gong, B., Hamilton, S. R., Hoopes, J. P., Jiang, Y., Kim, N., Mansfield, R., Nett, J. H., Rios, S., Strawbridge, R., Wildt, S. & Gerngross, T. U. (2006a) Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nature Biotechnology, 24, 210–215.

    PubMed  CAS  Google Scholar 

  • Li, L., Turatti, F., Crow, D., Bading, J. R., Anderson, A., Poku, E., Yazaki, P. J., Williams, L. E., Tamvakis, D., Sanders, P., Leong, D., Raubitschek, A., Hudson, P. J., Colcher, D. & Shively, J. E. (2010) Monodispersed DOTA-PEG-conjugated anti-TAG-72 diabody has low kidney uptake and high tumor-to-blood ratios resulting in improved 64Cu PET. Journal of Nuclear Medicine, 51, 1139–1146.

    PubMed  CAS  Google Scholar 

  • Li, L., Yazaki, P. J., Anderson, A., Crow, D., Colcher, D., Wu, A. M., Williams, L. E., Wong, J. Y. C., Raubitschek, A. & Shively, J. E. (2006c) Improved biodistribution and radioimmunoimaging with poly(ethylene glycol)-DOTA-conjugated anti-CEA diabody. Bioconjugate Chemistry, 17, 68–76.

    PubMed  CAS  Google Scholar 

  • Liu, M. A., Kranz, D. M., Kurnick, J. T., Boyle, L. A., Levy, R. & Eisen, H. N. (1985) Heteroantibody duplexes target cells for lysis by cytotoxic T lymphocytes. Proceedings of the National Academy of Sciences of the USA, 82, 8648–8652.

    PubMed  CAS  Google Scholar 

  • Liu, A. Y., Robinson, R. R., Hellstrom, K. E., Murray, E. D., Chang, C. P. & Hellstrom, I. (1987) Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. Proceedings of the National Academy of Sciences of the USA, 84, 3439–3443.

    PubMed  CAS  Google Scholar 

  • Lo, B. K. C. (2004) Antibody humanization by CDR grafting. In Lo, B.K.C. (Ed.) Methods in Molecular Biology. Totowa, NJ, Humana Press Inc, 248, 135–159.

    Google Scholar 

  • Lonberg, N. (2008) Fully human antibodies from transgenic mouse and phage display platforms. Current Opinion in Immunology, 20, 450–459.

    PubMed  CAS  Google Scholar 

  • Lonberg, N., Taylor, L. D., Harding, F. A., Trounstine, M., Higgins, K. M., Schramm, S. R., Kuo, C., Mashayekh, R., Wymore, K., Mccabe, J. G., Munoz-O’Regan, D., O’Donnell, S. L., Lapachet, E. S. G., Bengoechea, T., Fishwild, D. M., Carmack, C. E., Kay, R. M. & Huszar, D. (1994) Antigen-specific human antibodes from mice comprising four distinct genetic modifications. Nature, 368, 856–859.

    PubMed  CAS  Google Scholar 

  • Lund, J., Takahashi, N., Pound, J. D., Goodall, M., Nakagawa, H. & Jefferis, R. (1995) Oligosaccharide-protein interactions in IgG can modulate recognition by Fc gamma receptors. Federation of American Societies for Experimental Biology, 9, 115–119.

    CAS  Google Scholar 

  • Lutterbuese, R., Raum, T., Kischel, R., Hoffmann, P., Mangold, S., Rattel, B., Friedrich, M., Thomas, O., Lorenczewski, G., Rau, D., Schaller, E., Herrmann, I., Wolf, A., Urbig, T., Baeuerle, P. A. & Kufer, P. (2010) T cell-engaging BiTE antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer cells. Proceedings of the National Academy of Sciences of the USA, 107, 12605–12610.

    PubMed  CAS  Google Scholar 

  • Mack, M., Riethmuller, G. & Kufer, P. (1997) A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proceedings of the National Academy of Sciences of the USA, 92, 7021–7025.

    Google Scholar 

  • Marks, J. D., Hoogenboom, H., Bonnert, T. P., Mccafferty, J., Griffiths, A. D. & Winter, G. (1991) By-passing immunization: Human antibodies from V-gene libraries displayed on phage. Journal of Molecular Biology, 222, 581–597.

    PubMed  CAS  Google Scholar 

  • Marks, J. D., Hoogenboom, H. R., Griffiths, A. D. & Winter, G. (1992) Molecular evolution of proteins on filamentous phage. Journal of Biological Chemistry, 267, 16007–16010.

    PubMed  CAS  Google Scholar 

  • Martin, A. C. R. & Allen, J. (2007) Bioinformatics tools for antibody engineering. In Dubel, S. (Ed.) Handbook of Therapeutic Antibodies. Weinheim, Wiley-VCH.

    Google Scholar 

  • Martin, A. C. & Thornton, J. M. (1996) Structural families in loops of homologous proteins: Automatic classification, modelling and application to antibodies. Journal Molecular Biology, 263, 800–815.

    CAS  Google Scholar 

  • Mathew, M. & Verma, R. S. (2009) Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapy. Cancer Science, 100, 1359–1365.

    PubMed  CAS  Google Scholar 

  • Mazor, Y., Van Blarcom, T., Mabry, R., Iverson, B. L. & Georgiou, G. (2007) Isolation of engineered, full-length antibodies from libraries expressed in Escherichia coli. Nature Biotechnology, 25, 563–565.

    PubMed  CAS  Google Scholar 

  • Mccafferty, J., Griffiths, A. D., Winter, G. & Chiswell, D. (1990) Phage antibodies: Filamentous phage displaying antibody variable domains. Nature, 348, 552–554.

    PubMed  CAS  Google Scholar 

  • Menzel, C., Schirrmann, T., Hust, M., Konthur, Z., Jostock, T. & Dubel, S. (2008) Human antibody RNase fusion protein targeting CD30+ lymphomas. Blood, 111, 3830–3837.

    PubMed  CAS  Google Scholar 

  • Mian, I. S., Bradwell, A. R. & Olson, A. J. (1991) Structure, function and properfies of antibody binding sites. Journal of Molecular Biology, 217, 133–151.

    PubMed  CAS  Google Scholar 

  • Mikulski, S. M., Costanzi, J. J., Vogelzang, N. J., Mccachren, S., Taub, R. N., Chun, H., Mittelman, A., Panella, T., Puccio, C., Fine, R. & Shogen, K. (2001) Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. Journal of Clinical Oncology, 20, 274–281.

    Google Scholar 

  • Morgan, A., Jones, N. D., Nesbitt, A. M., Chaplin, L., Bodmer, M. W. & Emtage, J. S. (1995) The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, FcgammaRI and FcgammaRIII binding. Immunology, 86, 319–324.

    PubMed  CAS  Google Scholar 

  • Morrison, S. L., Johnson, M. J., Herzenberg, L. A. & Oi, V. T. (1984) Chimeric human antibody molecules: Mouse antigen-binding domains with human constant region domains. Proceedings of the National Academy of Sciences of the USA, 81, 6851–6855.

    PubMed  CAS  Google Scholar 

  • Muller, D., Karle, A., Meiburger, B., Hofig, I., Stork, R. & Kontermann, R. E. (2007) Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. Journal of Biological Chemistry, 282, 12650–12660.

    PubMed  Google Scholar 

  • Natsume, A., In, M., Takamura, H., Nakagawa, T., Shimizu, Y., Kitajima, K., Wakitani, M., Ohta, S., Satoh, M., Shitara, K. & Niwa, R. (2008) Engineered antibodies of IgG1/IgG3 mixed isotype with enhanced cytotoxic activities. Cancer Research, 68, 3863–3872.

    PubMed  CAS  Google Scholar 

  • Natsume, A., Niwa, R. & Satoh, M. (2009) Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC. Drug Design, Development and Therapy, 3, 7–16.

    PubMed  CAS  Google Scholar 

  • Newton, D. L., Hansen, H. J., Mikulski, S. M., Goldenberg, D. M. & Rybak, S. M. (2001) Potent and specific antitumor effects of an anti-CD22-targeted cytotoxin ribonuclease: Potential for the treatment of non-Hodgkin lymphoma. Blood, 97, 528–535.

    PubMed  CAS  Google Scholar 

  • Nguyen, A., Reyes, A. E., 2nd, Zhang, M., Mcdonald, P., Wong, W. L., Damico, L. A. & Dennis, M. S. (2006) The pharmacokinetics of an albumin-binding Fab (AB.Fab) can be modulated as a function of affinity for albumin. Protein Engineering, Design & Selection, 19, 291–7.

    CAS  Google Scholar 

  • Nicolaides, N. C., Ebel, W., Kline, B., Chao, Q., Routhier, E., Sass, P. M. & Grasso, L. (1995) Morphogenics as a tool for target discovery and drug development. Annals of the New York Academy of Sciences, 1059, 86–96.

    Google Scholar 

  • Nielsen, L. S., Baer, A., Müller, C., Gregersen, K., Mønster, N. T., Rasmussen, S. K., Weilguny, D. & Tolstrup, A. B. (2010) Single-batch production of recombinant human polyclonal antibodies. Molecular Biotechnology, 45, 257–266.

    PubMed  CAS  Google Scholar 

  • North, B. H., Lehmann, A. & Dunbrack, R. L. (2011) A new clustering of antibody loop conformations. Journal Moleculer Biology, 406, 228–256. doi:10.1016/j.jmb.2010.10.030. PMID 21035459.

    Google Scholar 

  • Ober, R. J., Martinez, C., Lai, X., Zhou, J. & Ward, E. S. (2004a) Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level. Proceedings of the National Academic of Sciences of the USA, 101, 11076–11081.

    CAS  Google Scholar 

  • Ober, R. J., Martinez, C., Vaccaro, C., Zhou, J. & Ward, E. S. (2004b) Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. Journal Immunology, 172, 2021–2029.

    CAS  Google Scholar 

  • Olsson, L., Andreasen, R. B., Ost, A., Christensen, B. & Biberfeld, P. (1984) Antibody producing human-human hybridomas II: Derivation and characterization of an antibody specific for human leukemia cells. Journal of Experimental Medicine, 159, 537–550.

    PubMed  CAS  Google Scholar 

  • Onda, M., Beers, R., Xiang, L., Nagata, S., Wang, Q. & Pastan, I. (2008) An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proceedings of the National Academy of Sciences of the USA, 105, 11311–11316.

    PubMed  CAS  Google Scholar 

  • Onda, M., Nagata, S., Fitzgerald, D. J., Beers, R., Fisher, R. J., Vincent, J. J., Lee, B., Nakamura, M., Hwang, J., Kreitman, R. J., Hassan, R. & Pastan, I. (2006) Characterization of the B cell epitopes associated with a truncated form of pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients. Journal of Immunology, 177, 8822–8834.

    CAS  Google Scholar 

  • Osada, T., Hsu, D., Hammond, S., Hobeika, A., Devi, G., Clay, T. M., Lyerly, H. K. & Morse, M. A. (2010) Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitve to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody. British Journal of Cancer, 102, 124–133.

    PubMed  CAS  Google Scholar 

  • Padlan, E. A. (1991) A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties. Molecular Immunology, 28, 489–498.

    PubMed  CAS  Google Scholar 

  • Pasut, G. & Veronese, F. M. (2009) PEG conjugates in clinical development or use as anticancer agents: An overview. Advanced Drug Delivery Reviews, 61, 1177–1188.

    PubMed  CAS  Google Scholar 

  • Persson, M. A. A., Caothien, R. H. & Burton, D. R. (1991) Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. Proceedings of the National Academy of Sciences of the USA, 88, 2432–2436.

    PubMed  CAS  Google Scholar 

  • Petersdorf, L., Kopecky, K., Stuart, R. K. & Al., E. (2009) Preliminary results of southwest oncology group study S0106L an international intergroup phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additiona therapy for previously untreated acute myeloid leukemia. Blood, 114, 790.

    Google Scholar 

  • Petkova, S. B., Akilesh, S., Sproule, T. J., Christianson, G. J., Khabbaz, H. A., Brown, A. C., Presta, L. G., Meng, Y. G. & Roopenian, D. C. (2006) Enhanced half-life of genetically engienered human IgG1 antibodies in a humanized FcRn mouse model: Potential application in humorally mediated autoimmune disease. International Immunology, 18, 1759–1769.

    PubMed  CAS  Google Scholar 

  • Posey, J. A., Khazaeli, M. B., Bookman, M. A., Nowrouzi, A., Grizzle, W. E., Thornton, J., Carey, D. E., Loenz, J. M., Sing, A. P., Siegall, C. B., Lobuglio, A. F. & Saleh, M. N. (2002) A phase I trial of the single-chain immunotixin SGN-10 (BR96 scFv-PE40) in patients with advanced solid tumors. Clinical Cancer Research, 8, 3092–3099.

    PubMed  CAS  Google Scholar 

  • Raghavan, M. & Bjorkman, P. J. (1996) Fc receptors and their interactions with immunoglobulins. Annual Review of Cell and Developmental Biology, 12, 181–220.

    PubMed  CAS  Google Scholar 

  • Raju, T. S. (2003) Glycosylation variations with expression systems and their impact on biological activity of therapeutic immunoglobulins. Bioprocess International, 1, 44–53.

    CAS  Google Scholar 

  • Reiter, Y. & Pastan, I. (1998) Recombinant Fv immunotoxins and Fv fragments as novel agents for cancer therapy and diagnosis. Trends in Biotechnology, 16, 513–520.

    PubMed  CAS  Google Scholar 

  • Riechmann, L., Clark, M., Waldmann, H. & Winter, G. (1988) Reshaping human antibodies for therapy. Nature, 332, 323–327.

    PubMed  CAS  Google Scholar 

  • Risberg, K., Fodstad, O. & Andersson, Y. (2010) Immunotoxins: A promising treatment modality for metastatic melanoma? Ochsner Journal, 10, 193–199.

    Google Scholar 

  • Robinson, M. K., Alpaugh, R. K. & Borghaei, H. (2010) Naptumomab estafenatox: A new immunoconjugate. Expert Opinion on Biological Therapy, 10, 273–9.

    PubMed  CAS  Google Scholar 

  • Roguska, M. A., Pedersen, J. T., Henry, A. H., Searle, S. M. J., Roja, C. M., Avery, B., Hoffee, M., Cook, S., Lamber, J. M., Blattler, W. A., Rees, A. R. & Guild, B. C. (1996) A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing. Protein Engineering, 9, 895–904.

    PubMed  CAS  Google Scholar 

  • Roscoe, D. M., Pai, L. H. & Pastan, I. (1997) Identification of epitopes on a mutant form of Pseudomonas exotoxin using serum from humans treated with Pseudomonas exotoxin containing immunotoxins. European Journal of Immunology, 27, 1459–1468.

    PubMed  CAS  Google Scholar 

  • Rosok, M. J., Yelton, D. E., Harris, L. J., Bajorath, J., Hellstrom, K. E., Hellstrom, I., Cruz, G. A., Kristensson, K., Lin, H., Huse, W. D. & Glaser, S. M. (1996) A combinatorial library strategy for the rapid humanization of anticarcinoma BR96 Fab. Journal Biology Chemistry, 271, 22611–22618.

    CAS  Google Scholar 

  • Rothe, C., Ulrlinger, S., Lohning, C., Prassler, J., Stark, Y., Jager, U., Hubner, B., Bardroff, M., Pradel, I., Boss, M., Bittlingmaier, R., Bataa, T., Frisch, C., Brocks, B., Honegger, A. & Urban, M. (2008) The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies. Journal of Molecular Biology, 376, 1182–1200.

    PubMed  CAS  Google Scholar 

  • Saldanha, J. W. (2009) Humanization of Recombinant Antibodies. New York, NY, Cambridge University Press.

    Google Scholar 

  • Saldanha, J. W., Martin, A. C. & Leger, O. J. (1999) A single backmutation in the human kIV framework of a previously unsuccessfully humanized antibody restores the binding activity and increases the secretion in cos cells. Molecular Immunology, 36, 709–719.

    PubMed  CAS  Google Scholar 

  • Salfeld, J. G. (2007) Isotype selection in antibody egineering. Nature Biotechnology, 25, 1369–1372.

    PubMed  CAS  Google Scholar 

  • Salfeld, J. G., Allen, D. J., Hoogenboom, H. R. J. M., Kaymakcalan, Z., Labkovsky, B., Mankovich, J. A., Cfuinness, B. T., Roberts, A. J., Sakorafas, P., Schoenhaut, D., Vaughan, T. J., White, M. & Wilton, A. J. (2000) Human antibodies that bind human TNFalpha, patent number US 6258562 B1, 10, July 2001.

    Google Scholar 

  • Salfeld, J. G., Zaymakcalan, Z., Tracey, D., Roberts, A. & Kamen, R. (1998) Generation of fully human anti-TNF antibody D2E7 [Abstract]. Arthritis and Rheumetism, 41, S57.

    Google Scholar 

  • Santanche, S., Bellelli, A. & Brunori, M. (1997) The unusual stability of saporin, a candidate for the synthesis of immunotoxins. Biochemical and Biophysical Research Communications, 234, 129–132.

    PubMed  CAS  Google Scholar 

  • Schirrmann, T. & Hust, M. (2010) Construction of human antibody gene libraries and selection of antibodies by phage display. In Yotnda, P. (Ed.) Immunotherapy of Cancer. New York, NY, Humana Press.

    Google Scholar 

  • Schmidt, M. M. & Wittrup, K. D. (2009) A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Molecular Cancer Therapy, 8, 2861–2871.

    CAS  Google Scholar 

  • Schroff, R. W., Foon, K. A., Beatty, S. M., Oldham, R. K. & Morgan, A. C. (1985) Human anti-murine immunoglobulin in response in patients receiving monoclonal antibody therapy. Cancer Research, 45, 879–885.

    PubMed  CAS  Google Scholar 

  • Schwarz, F., Huang, W., Li, C., Schulz, B. L., Lizak, C., Palumbo, A., Numao, S., Neri, D., Aebi, M. & Wang, L. X. (2010) A combined method for producing homogeneous glycoproteins with eukaryotic N-glycosylation. National Chemistry Biology, 6, 264–266.

    CAS  Google Scholar 

  • Shawler, D. L., Bartholomew, R. M., Smith, L. M. & Dillman, R. O. (1985) Human immune response to multiple injections of murine monoclonal IgG1. Journal of Immunology, 135, 1530–1535.

    CAS  Google Scholar 

  • Shields, R. L., Lai, J., Keck, R., O’Connell, L. Y., Hong, K., Meng, Y. G., Weikert, S. H. A. & Presta, L. G. (2002) Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcgammaRIII and antibody-dependent cellular toxicity. Journal of Biological Chemistry, 277, 36733–36740.

    Google Scholar 

  • Shields, R. L., Namenuk, A. K., Hong, K., Meng, Y. G., Rae, J., Briggs, J., Xie, D., Lai, J., Stadlen, A., Li, B., Fox, J. A. & Presta, L. G. (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. Journal Biology Chemistry, 276, 6591–6604.

    CAS  Google Scholar 

  • Sikora, K., Alderson, T., Ellis, J., Phillips, J. & Watson, J. (1983) Human hybridomas from patients with malignant disease. British Journal of Cancer, 47, 135–145.

    PubMed  CAS  Google Scholar 

  • Smith, G. P. (1985) Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. GP Smith, 228, 1315–1317.

    CAS  Google Scholar 

  • Sola, R. J. & Griebenow, K. (2010) Glycosylation of therapeutic proteins: An effective strategy to optimize efficacy. BioDrugs, 24, 9–21.

    PubMed  CAS  Google Scholar 

  • Sola, R. J., Rodriguez-Martinez, J. A. & Griebenow, K. (2007) Modulation of protein biophysical properties by chemical glycosylation: Biochemical insights and biomedical implications. Cellular and Molecular Life Sciences, 64, 2133–2152.

    PubMed  CAS  Google Scholar 

  • Steinitz, M., Klein, G., Koskimies, S. & Makel, O. (1977) EB virus-induced B lymphocyte cell lines producing specific antibody. Nature, 269, 420–422.

    PubMed  CAS  Google Scholar 

  • Tan, A. R., Moore, D. F., Hidalgo, M., Doroshow, J. H., Poplin, E. A., Goodin, S., Mauro, D. & Rubin, E. H. (2006) Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors. Clinical Cancer Research, 12, 6517–6522.

    PubMed  CAS  Google Scholar 

  • Tangri, S., Mothe, B. R., Eisenbraun, J., Sidney, J., Southwood, S., Briggs, K., Zinckgraf, J., Newman, M., Chesnut, R., Licalsi, C. & Sette, A. (2005) Rationally engineered therapeutic proteins with reduced immunogenicity. Journal of Immunology, 174, 3187–3196.

    CAS  Google Scholar 

  • Teng, N. N. H., Lam, K. S., Riera, F. C. & Kaplan, H. S. (1983) Construction and testing of mouse-human heteromyelomas for human monoclonal antibody production. Proceedings of the National Academy of Sciences of the USA, 80, 7308–7312.

    PubMed  CAS  Google Scholar 

  • Todorovska, A., Roovers, R. C., Dolezal, O., Kortt, A. A., Hoogenboom, H. R. & Hudson, P. J. (2001) Design and application of diabodies, triabodies and tetrabodies for cancer targeting. Journal of Immunological Methods, 248, 47–66.

    PubMed  CAS  Google Scholar 

  • Tolcher, A. W., Ochoa, L., Hammond, L. A., Patnaik, A., Edwards, T., Takimoto, C., Smith, L., De Bono, J., Schwartz, G., Mays, T., Jonak, Z. L., Johnson, R., Dewitte, M., Martino, H., Audette, C., Maes, K., Chari, R. V., Lambert, J. M. & Rowinsky, E. K. (2003) Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: A phase I, pharmacokinetic, and biologic correlative study. Journal Clinical Oncology, 21, 211–222.

    CAS  Google Scholar 

  • Trussel, S., Dumelin, C., Frey, K., Villa, A., Buller, F. & Neri, D. (2009) New strategy for the extension of the serum half-life of antibody fragments. Bioconjugate Chemistry, 20, 2286–2292.

    PubMed  CAS  Google Scholar 

  • Tsutsumi, Y., Onda, M., Nagata, S., Lee, B., Kreitman, R. J. & Pastan, I. (2000) Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity. Proceedings of the National Academy of Sciences of the USA, 97, 8548–8553.

    PubMed  CAS  Google Scholar 

  • Umana, P., Jean-Mairet, J., Moudry, R., Amstutz, H. & Bailey, J. E. (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nationl Biotechnology, 17, 176–180.

    CAS  Google Scholar 

  • Vaccaro, C., Zhou, J., Ober, R. J. & Ward, E. S. (2005) Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. National Biotechnology, 23, 1283–1288.

    CAS  Google Scholar 

  • Van Cutsem, E., Peeters, M., Siena, S., Humblet, Y., Hendlisz, A., Neyns, B., Canon, J. L., Van Laethem, J. L., Maurel, J., Richardson, G., Wolf, M. & Amado, R. G. (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. Journal of Clinical Oncology, 25, 1658–1664.

    PubMed  Google Scholar 

  • Van Meerten, T., Van Rijn, R. S., Hol, S., Hagenbeek, A. & Ebeling, S. B. (2006) Complement-induced cell death by Rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular toxicity. Clinical Cancer Research, 12, 4027–4035.

    PubMed  Google Scholar 

  • Vegarud, G. & Christensen, T. B. (1975) The resistance of glycoproteins to proteolytic inactivation. Acta Chemica Scandinavica B, 29, 887–888.

    CAS  Google Scholar 

  • Vogel, C. L., Burris, H. A., Limentani, S., Borson, R., O’Shaughnessy, J., Vukelja, S., Agresta, S., Klencke, B., Birkner, M. & Rugo, H. (2009) A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results. Journal Clinical Oncology, 27, 1017.

    Google Scholar 

  • Weinblatt, M. E., Keystone, E. C., Furst, D. E., Moreland, L. W., Weisman, M. H., Birbara, C. A., Teoh, L. A., Fischkoff, S. A. & Chartash, E. K. (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate. Arthritis and Rheumetism, 48, 35–45.

    CAS  Google Scholar 

  • Weiner, L. M., Blelldegrun, A. S., Crawford, J., Tolcher, A. W., Lockbaum, P., Arends, R. H., Anavale, L., Amado, R. G., Schwab, G. & Figlin, R. A. (2008) Dose and schedule study of Panitumumab monotherapy in patients with advanced solid malignancies. Clinical cancer Research, 14, 502–508.

    PubMed  CAS  Google Scholar 

  • Weiner, L. M., Holmes, M., Richeson, A., Godwin, A., Adams, G. P., Hsieh-Ma, S. T., Ring, D. B. & Alpaugh, R. K. (1993) Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1. Journal of Immunology, 151, 2877–2886.

    CAS  Google Scholar 

  • Wochner, R. D., Strober, W. & Waldmann, T. A. (1967) The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments. Journal of Experimental Medicine, 126, 207–221.

    PubMed  CAS  Google Scholar 

  • Wolf, E., Hofmeister, R., Kufer, P., Schlereth, B. & Baeuerle, P. A. (2005) BiTEs: Bispecific antibody constructs with unique anti-tumor activity. Drug Discovery Today, 10, 1237–1244.

    PubMed  CAS  Google Scholar 

  • Wright, A. & Morrison, S. L. (1994) Effect of altered CH2-associated carbohydrate structure on the funcitonal properties and in vivo fate of chimeric mouse-human immunoglobulin G1. Journal of Experimental Medicine, 180, 1087–1096.

    PubMed  CAS  Google Scholar 

  • Yazaki, P. J., Kassa, T., Cheung, C., Crow, D. M., Sherman, M. A., Bading, J. R., Anderson, A. J., Colcher, D. & Raubitschek, A. (2008) Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein. Nuclear Medicine and Biology, 35, 151–158.

    PubMed  CAS  Google Scholar 

  • Yokota, T., Milenic, D. E., Whitlow, M. & Schlom, J. (1992) Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Research, 52, 3402–3408.

    PubMed  CAS  Google Scholar 

  • Youn, Y. S., Na, D. H., Yoo, S. D., Song, S. & Lee, K. C. (2005) Carbohydrate-specifically polyethylene glycol-modified ricin A-chain with improved therapeutic potential. International Journal of Biochemistry and Cell Biology, 37, 1525–1533.

    PubMed  CAS  Google Scholar 

  • Zalevsky, J., Chamberlain, A. K., Horton, H. M., Karki, S., Leung, I. W. L., Sproule, T. J., Lazar, G. A., Roopenian, D. C. & Desjarlais, J. R. (2010) Enhanced anitbody half-life improves in vivo activity. Nature Biotechnology, 28, 157–159.

    PubMed  CAS  Google Scholar 

  • Zent, C. S., Secreto, C. R., Laplant, B. R., Bone, N. D., Call, T. G., Shanafelt, T. D., Jelinek, D. F., Tschumper, R. C. & Kay, N. E. (2008) Direct and complement dependent cytotoxicity in CLL cells from patients with high risk early stage chronic lyphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leukemia Research, 32, 1849–1856.

    PubMed  CAS  Google Scholar 

  • Zhu, H., Yang, B., Yang, X., Wang, L., Xu, J., Liao, C., Feng, Q., Tang, H., Hu, L., Chen, Z. & Li, Y. (2009) A novel antibody fragment targeting HAb18G/CD147 with cytotoxicity and decreased immunogenicity. Cancer Biology & Therapy, 8, 1035–1044.

    CAS  Google Scholar 

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  1. Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Lisa E. Goldsmith & Matthew K. Robinson

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  1. Lisa E. Goldsmith
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  1. Dept. Chemical & Biochemical, Engineering, University College, Dublin, Belfield, Dublin 4, Ireland

    Mohamed Al-Rubeai

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Goldsmith, L.E., Robinson, M.K. (2011). Engineering Antibodies for Cancer Therapy. In: Al-Rubeai, M. (eds) Antibody Expression and Production. Cell Engineering, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1257-7_10

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