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Recent Developments in the Construction of Bispecific Antibodies

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Book cover Alternative Approaches to Human Blood Resources in Clinical Practice

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 33))

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Abstract

Current systemic anti-cancer therapies largely depend upon the cytotoxic effect of the drug(s) on tumour cells versus a more restricted cytotoxic effect on nontumour cells. This inherently limited targeting specificity may lead to unacceptable toxicity at therapeutic doses, thus restricting the available “therapeutic window”. Already at the beginning of this century Ehrlich envisioned that immunoglobulins (Ig) or antibodies (Ab) can specifically deliver cytotoxic reagents to tumour cells to eradicate these cells. This idea was called the “magic bullet” concept [1].

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References

  1. Kaminski MS, Zasadny KR, Francis IR, et al. Radioimmunotherapy of B-cell lymphoma with [131] anti-Bl (anti-CD20) antibody. N Engl J Med 1993;329:459–465.

    Article  PubMed  CAS  Google Scholar 

  2. Schroff RW, Foon KA, Beatty SM, Oldham RK, Morgan AC Jr. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res 1985;45:879–885.

    PubMed  CAS  Google Scholar 

  3. De Leij L. Tumor and differentiation antigens. In: Bertino JR (ed). Encyclopedia of Cancer. San Diego: Academic Press Inc. 1997:p1818–1839.

    Google Scholar 

  4. De Leij L, Helfrich W, Stein F, Mattes MJ. SCLC-cluster-2 antibodies detect the pancarcinoma/epithelial glycoprotein EGP-2. Int J Cancer 1994;57(suppl 8):60–63.

    Article  Google Scholar 

  5. Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res 1987;47:2883–2891.

    PubMed  CAS  Google Scholar 

  6. Edwards DP, Grzyb KT, Dressler LG. Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer. Cancer Res 1986;46:1306–1317.

    PubMed  CAS  Google Scholar 

  7. Varki NM, Reisfeld PA, Walker LE. Antigens associated with a human lung adeno-carcinoma defined by monoclonal antibodies. Cancer Res 1984;44:681–687.

    PubMed  CAS  Google Scholar 

  8. Bumol TF, Marder P, DeHerdt SV, Borowitz MJ, Apelgren LD. Characterization of the human tumor and normal tissue reactivity of the KSI/4 monoclonal antibody. Hy-bridoma 1988;7:407–415.

    CAS  Google Scholar 

  9. Spurr NK, Durbin H, Sheer D, Parkar M, Bobrow L, Bodmer WF. Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI. Int J Cancer 1986;38:631–636.

    Article  PubMed  CAS  Google Scholar 

  10. Riethmuller G, Schneider-Gadicke E, Schlimok G, et al. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. German Cancer Aid 17-IA Study Group [see comments]. Lancet 1994;343:1177–1183.

    Article  PubMed  CAS  Google Scholar 

  11. Elias DJ, Ibrschowitz L, Kline LE, et al. Phase 1 clinical comparative study of monoclonal antibody KS 1/4 and KS 1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma. Cancer Res 1990;50:4154–4159.

    PubMed  CAS  Google Scholar 

  12. Kosterink J, De Jonge M, Smith E, et al. Pharmacokinetics and scintigraphy of in-dium-lll-DTPA-MOC-31 in small-cell lung carcinoma. J Nucl Med 1995;36:2356–2362.

    PubMed  CAS  Google Scholar 

  13. Spearman ME, Goodwin RM, Kau D. Disposition of the monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB (LY256787), in Fischer 344 rats and rhesus monkeys. Drug Metab Dispos Biol Fate Chem 1987; 15:640–647.

    PubMed  CAS  Google Scholar 

  14. Apelgren LD, Zimmerman DL, Briggs SL, Bumol TF. Antitumor activity of the monoclonal antibody-Vinca alkaloid immunoconjugate LY203725 (KSl/4-4-des-acetylvinblastine-3-carboxhydrazide) in a nude mouse model of human ovarian cancer. Cancer Res 1990;50:3540–3544.

    PubMed  CAS  Google Scholar 

  15. Schneck D, Butler F, Dugan W, et al. Disposition of a murine monoclonal antibody vinca conjugate (KS1/4-DAVLB) in patients with adenocarcinomas. Clin Pharmacol Ther 1990;47:36–41.

    Article  PubMed  CAS  Google Scholar 

  16. Carter P, Rodrigues ML, Lewis GD, Figari I, Shalaby N1R. Towards an immuno-therapy for pl85HER2 overexpressing tumors. Adv Exp Med Biol 1994;353:83–94.

    Article  PubMed  CAS  Google Scholar 

  17. Huang X, Molema G, King S, Watkins L, Edgington TS, Thorpe PE. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 1997;275:547–550.

    Article  PubMed  CAS  Google Scholar 

  18. Digiesi G, Giacomini P, Fraioli R, et al. Production and characterization of murine mabs to the extracellular domain of human neu oncogene product GP185HER2. Hybridoma 1992;11:519–527.

    Article  PubMed  CAS  Google Scholar 

  19. Heijnen I A, Van de Winkel JG. A human Fc gamma RI/CD64 transgenic model for in vivo analysis of (bispecific) antibody therapeutics. J Hematother 1995;4(5):351–356.

    Article  PubMed  CAS  Google Scholar 

  20. Fanger MW, Morganelli PM, Guyre PM. Bispecific antibodies. Crit Rev Immunol 1992;12(3-4):101–124.

    PubMed  CAS  Google Scholar 

  21. Kroesen BJ, Buter J, Sleijfer DT, et al. Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2. Br J Cancer 1994;70:652–661.

    Article  PubMed  CAS  Google Scholar 

  22. Kroesen BJ, ter Haar A, Spakman H, et al. Local antitumour treatment in carcinoma patients with bispecific-monoclonal-antibody-redirected T cells. Cancer Immunol Immunother 1993;37:400–407.

    Article  PubMed  CAS  Google Scholar 

  23. Kroesen BJ, Helfrich W, Bakker A, et al. Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody-redirected T cells in an immunocompetent rat model. Int J Cancer 1995;61:812–818.

    Article  PubMed  CAS  Google Scholar 

  24. McCafferty J, Griffiths AD, Winter G, Chiswell DJ. Phage antibodies: filamentous phage displaying antibody variable domains. Nature 1990;348:552–554.

    Article  PubMed  CAS  Google Scholar 

  25. Orlandi R, Gussow DH, Jones PT, Winter G. Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci USA 1989;86:3833–3837.

    Article  PubMed  CAS  Google Scholar 

  26. Hoogenboom M, Griffiths AD, Johnson KS, Chisweil DJ, Hudson P, Winter G. Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Res 1991; 19:4133–4137.

    Article  PubMed  CAS  Google Scholar 

  27. Clackson T, Hoogenboom M, Griffiths AD, Winter G. Making antibody fragments using phage display libraries. Nature 1991;352:624–628.

    Article  PubMed  CAS  Google Scholar 

  28. Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR. Making antibodies by phage display technology. Annu Rev Immunol 1994:12:433–455.

    Article  PubMed  CAS  Google Scholar 

  29. Marks JD, Hoogenboom M, Bonnert TP, McCafferty J, Griffiths AD, Winter G. Bypassing immunization. Human antibodies from V-gene libraries displayed on phage. J Mol Biol 1991;222:581–597.

    Article  PubMed  CAS  Google Scholar 

  30. Hoogenboom HR, Winter G. By-passing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro. J Mol Biol 1992;227:381–388.

    Article  PubMed  CAS  Google Scholar 

  31. Gruber M, Schodin BA, Wilson ER, Kranz DM. Efficient tumor cell lysis mediated by a bispecific single chain antibody expressed in Escherichia coli. J Immunol 1994;152:5368–5374.

    PubMed  CAS  Google Scholar 

  32. Traunecker A, Lanzavecchia A, Karjalainen K. Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells. EMBO J 1991; 10: 3655–3659.

    PubMed  CAS  Google Scholar 

  33. Jost CR, Titus JA, Kurucz I, Segal DM. A single-chain bispecific Fv-2 molecule produced in mammalian cells redirects lysis by activated CTL. Molecular Immunology 1996;33:211–219.

    Article  PubMed  CAS  Google Scholar 

  34. Mack M, Riethmuller G, Kufer P. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc Natl Acad Sci USA 1995;92:7021–7025.

    Article  PubMed  CAS  Google Scholar 

  35. Mack M, Gruber P, Schmidt S, Riethmuller G, Kufer P. Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity. J Immunol 1997; 1997 Aprl 5;158:3965–3970.

    PubMed  CAS  Google Scholar 

  36. Roder JC, Cole SP, Kozbor D. The EBV-hybridoma technique. Methods Enzymol 1986; 121:140–167.

    Article  PubMed  CAS  Google Scholar 

  37. Whitlow M, Filpula D, Rollence ML, Feng SL, Wood JF. Multivalent Fvs: characterization of single-chain Fv oligomers and preparation of a bispecific Fv. Protein Eng 1994;7:1017–1026.

    Article  PubMed  CAS  Google Scholar 

  38. Holliger P, Prospero T, Winter G. “Diabodies”: small bivalent and bispecific antibody fragments. Proc Natl Acad Sci USA 1993;90:6444–6448.

    Article  PubMed  CAS  Google Scholar 

  39. Perisic O, Webb PA, Holliger P, Winter G. Williams RL. Crystal structure of a diabody, a bivalent antibody fragment. Structure 1994;2:1217–1226.

    Article  PubMed  CAS  Google Scholar 

  40. Holliger P, Brissinck J, Williams RL, Thielemans K, Winter G. Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody. Protein Eng 1996;9:299–305.

    Article  PubMed  CAS  Google Scholar 

  41. Wu AM, Chen W, Raubitschek A, Tumor localization of anti-CEA single-chain Fvs: improved targetting by non-covalent dimers. Immunotechnology. Immunotechnology 1996;221–236.

    Google Scholar 

  42. Fitzgerald K, Holliger P, Winter G. Improved tumour targeting by disulphide stabilized diabodies expressed in Pichia pastoris. Protein Eng 1997; 10:1221–1225.

    Article  PubMed  CAS  Google Scholar 

  43. Zhu Z, Zapata G, Shalaby R, Snedecor B, Chen H, Carter P. High level secretion of a humanized bispecific diabody from Escherichia coli. Bio-Technology 1996;(New York): 192–196.

    Google Scholar 

  44. Iliades P, Kortt AA, Hudson PJ. Triabodies: Single chain Fv fragments without a linker form trivalent trimers. Febs Letters 1997;409:437–441.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. W. Helfrich
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  2. B. J. Kroesen
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  3. G. Molema
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  4. L. de Leij
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Editor information

Editors and Affiliations

  1. Red Cross Blood Bank Noord Nederland, The Netherlands

    C. Th. Smit Sibinga  & P. C. Das  & 

  2. C.L. Mclntosh & Ass., Rockville, MD, USA

    J. C. Fratantoni

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© 1998 Springer Science+Business Media Dordrecht

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Helfrich, W., Kroesen, B.J., Molema, G., de Leij, L. (1998). Recent Developments in the Construction of Bispecific Antibodies. In: Sibinga, C.T.S., Das, P.C., Fratantoni, J.C. (eds) Alternative Approaches to Human Blood Resources in Clinical Practice. Developments in Hematology and Immunology, vol 33. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5619-0_10

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  • DOI: https://doi.org/10.1007/978-1-4615-5619-0_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7571-5

  • Online ISBN: 978-1-4615-5619-0

  • eBook Packages: Springer Book Archive

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