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Antibodies pp 169-182 | Cite as

Expression of Recombinant Antibodies by Tumour Cells: On Road to Anti-Tumour Therapy

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Abstract

Monoclonal antibodies are attractive tools for cancer therapy and have now come of age as therapeutics. Their exquisite specificity, combined with their ability to activate potent effector functions makes them an ideal tool for cancer therapy. Depending on their classes and subclasses, antibodies can activate complement and/or trigger effector functions such as Antibody-Dependent Cell Cytotoxicity (ADCC) following interactions with the receptors for the Fc region of IgG or IgA (FcγR and FcαR). Over the last decade, therapeutic antibodies have moved to the forefront of protein drug development, mostly due to the formidable capacity to engineer their immunogenicity, their affinity and their functions (Mehren et al., 2003). Therapeutic monoclonal antibodies are currently being used to target either soluble circulating molecules such as cytokines or cell surface antigens following systemic delivery. They also represent exciting tools for the targeted delivery of drugs, enzymes, and toxins at the site of the tumours. In addition, antibody-based radio-immunotherapy (RIT) should make it possible to circumvent the limitation of the treatment of solid tumours with antibodies due to the weak penetration of intact antibody molecules.

Keywords

Recombinant Antibody Chloramphenicol Acetyl Transferase Bispecific Antibody Nuclear Localisation Signal Sequence Chloramphenicol Acetyl Transferase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Armstrong, T.D., Clements, V.K., Martin, B.K., Ting, J.P., and Ostrand-Rosenberg, S., 1997, Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity. Proc. Natl. Acad. Sci. USA 94: 6886–6891PubMedCrossRefGoogle Scholar
  2. Bai, J., Sui, J., Zhu, R.Y., Tallarico, A.S., Gennari, F., Zhang, D., and Marasco, W.A., 2003, Inhibition of Tat-mediated transactivation and HIV-1 replication by human anti-hCyclinTl intrabodies. J. Biol. Chem. 278: 1433–1442PubMedCrossRefGoogle Scholar
  3. Bilbao, G., Contreras, J.L., and Curiel, D.T., 2002, Genetically engineered intracellular single-chain antibodies in gene therapy. Mol. Biotechnol. 22: 191–211PubMedCrossRefGoogle Scholar
  4. Biocca, S., Neuberger, M.S., and Cattaneo, A., 1990, Expression and targeting of intracellular antibodies in mammalian cells. The EMBO J. 9: 101–108Google Scholar
  5. Cardinale, A., Filesi, I., and Biocca, S., 2001, Aggresome formation by anti-Ras intracellular scFv fragments. The fate of the antigen-antibody complex. Eur. J. Biochem. 268: 268–277PubMedCrossRefGoogle Scholar
  6. Caron de Fromentel, C., Gruel, N., Venot, C., Debussche, L., Conseiller, E., Dureuil, C., Teillaud, J.-L., Tocqué, B., and Bracco, L., Restoration of transcriptional activity of p53 mutants in human tumor cells by intracellular expression of anti-p53 single chain Fv fragments. Oncogene, 1999, 18: 551–557PubMedCrossRefGoogle Scholar
  7. Cochet, O., Delumeau, I., Königsberg, M., Gruel, N., Schweighoffer, F., Bracco, L., Teillaud, J.-L., and Tocqué, B., 1998a, Intracellular targeting of oncogenes: a novel approach for cancer therapy. In Intrabodies (W.A. Marasco, ed.), Landes R.G. Company, Chapman & Hall, New York, pp. 129–142Google Scholar
  8. Cochet, O., Kenigsberg, M., Delumeau, I., Virone-Oddos, A., Multon, M.-C., Fridman, W.H., Schweighoffer, F., Teillaud, J.-L., and Tocqué, B., 1998b, Intracellular expression of an antibody fragment neutralizing p21ras promotes tumor regression. Cancer Res. 58: 1170–1176Google Scholar
  9. Cochet, O., Kenigsberg, M., Delumeau, I., Duchesne, M., Schweighoffer, F., Tocqué, B., and Teillaud, J.-L., 1998c, Intracellular expression and functional properties of an anti-p21ras scFv derived from a rat hybridoma containing specific λ and irrelevant κ light chains. Mol. Immunol. 35: 1097–1110Google Scholar
  10. Cohen, P.A., 2002, Intrabodies. Targeting scFv expression to eukaryotic intracellular compartments. Methods Mol. Biol. 178: 367–378PubMedGoogle Scholar
  11. Curiel, D.T., 2000, Gene therapy for carcinoma of the breast: genetic ablation strategies. Breast Cancer Res. 2: 45–49PubMedCrossRefGoogle Scholar
  12. Dauvillier, S., Merida, P., Visintin, M., Cattaneo, A., Bonnerot, C., and Dariavach, P., 2002, Intracellular single-chain variable fragments directed to the Src homology 2 domains of Syk partially inhibit FcεRI signaling in the RBL-2H3 cell line. J. Immunol. 169: 2274–2283PubMedGoogle Scholar
  13. Gansbacher, B., Bannerji, R., Daniels, B., Zier, K., Cronin, K., and Gilboa, E., 1990, Retroviral vector-mediated γ-interferon gene transfer into tumor cells generates potent and long lasting anti-tumor immunity. Cancer Res. 50: 7820–7825PubMedGoogle Scholar
  14. Gruel, N., Fridman, W.H., and Teillaud, J.-L., 2001, By-passing tumor-specific and bispecific antibodies: triggering of antitumor immunity by expression of anti-FcγR scFv on cancer cell surface. Gene Therapy 8: 1721–1728PubMedCrossRefGoogle Scholar
  15. Guarini, A., Gansbacher, B., Cronin, K., Fierro, M.T., and Foa, R., 1995, IL-2 gene-transduced human HLA-A2 melanoma cells can generate a specific anti-tumor cytotoxic T-lymphocyte response. Cytokines & Mol. Ther. 1: 57–64Google Scholar
  16. Hulett, M.D., and Hogarth, P.M., 1994, Molecular basis of Fc receptor function. Adv. Immunol. 57: 1–127PubMedCrossRefGoogle Scholar
  17. Hupp, T.R., Meek, D.W., Midgley, CA., Lane, D.P., 1992, Regulation of the specific DNA binding function of p53. Cell 71: 875–886PubMedCrossRefGoogle Scholar
  18. Hupp, T.R., Meek, D.W., Midgley, CA., Lane, D.P., 1993, Activation of the cryptic DNA binding function of mutant forms of p53. Nucleic Acids Res. 21: 3167–3174PubMedCrossRefGoogle Scholar
  19. Hurwitz, A.A., Townsend, S.E., Yu, T.F., Wallin, J.A., and Allison, J.P., 1998, Enhancement of the anti-tumor immune response using a combination of interferon-γ and B7 expression in an experimental mammary carcinoma. Int. J. Cancer 77: 107–113PubMedCrossRefGoogle Scholar
  20. Hwu, P., Yang, J.C., Cowherd, R., Treisman, J., Shafer, G.E., Eshhar, Z., and Rosenberg, S.A., 1995, In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. Cancer Res. 55: 3369–3373PubMedGoogle Scholar
  21. Imro, M.A., Dellabona, P., Manici, S., Heltai, S., Consogno, G., Bellone, M., Rugarli, C., and Protti, M.P., 1998, Human melanoma cells transfected with the B7-2 co-stimulatory molecule induce tumor-specific CD8+ cytotoxic T lymphocytes in vitro. Human Gene Ther. 9: 1335–1344CrossRefGoogle Scholar
  22. Kalergis, A.M., and Ravetch, J.V., 2002, Inducing tumor immunity through the selective engagement of activating Fcγ receptors on dendritic cells. J. Exp. Med. 195: 1653–1659PubMedCrossRefGoogle Scholar
  23. Kontermann, R.E., and Muller, R. 1999, Intracellular and cell surface displayed single-chain diabodies. J. Immunol. Methods 22: 179–188CrossRefGoogle Scholar
  24. Lecerf, J.M., Shirley, T.L., Zhu, Q., Kazantsev, A., Amersdorfer, P., Housman, D.E., Messer, A., and Huston, J.S., 2001, Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington’s disease. Proc. Natl Acad. Sci. USA 98: 4764–4769PubMedCrossRefGoogle Scholar
  25. Marasco, W.A., Haseltine, W.A., and Chen, S.Y., 1993, Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp 120 single-chain antibody. Proc. Natl. Acad. Sci. USA 90: 7427–7429CrossRefGoogle Scholar
  26. Marasco, W.A., 2001, Intrabodies as antiviral agents. Curr. Top. Microbiol. Immunol. 260: 247–270PubMedGoogle Scholar
  27. Mehren, Mv.M., Adams, G.P., and Weiner, L.M., 2003, Monoclonal antibody therapy for cancer. Annu. Rev. Med. 54: 343–369CrossRefGoogle Scholar
  28. Mhashilkar, A.M., Bagley, J., Chen, S.Y., Szilvay, A.M., Heiland, D.G., Marasco, W.A., 1995, Inhibition of HIV-1 Tat-mediated LTR transactivation and HIV-1 infection by anti-Tat single chain intrabodies. EMBO J. 14: 1542–1551PubMedGoogle Scholar
  29. Michon, J., Moutel, S., Barbet, J., Romet-Lemonne, J.-L., Deo, Y.M., Fridman, W.H., Teillaud, J.-L., 1995, In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-FcγRI bispecific antibody. Blood 86: 1124–1130PubMedGoogle Scholar
  30. Mingari, M.C., Moretta, A., Moretta, L., 1998, Regulation of KIR expression in human T cells: a safety mechanism that may impair protective T-cell responses. Immunol. Today 19: 153–157PubMedCrossRefGoogle Scholar
  31. Nizak, C., Monier, S., del Nery, E., Moutel, S., Goud, B., and Perez, F., 2003, Recombinant antibodies to the small GTPase Rab6 as conformation sensors. Science 300: 984–987PubMedCrossRefGoogle Scholar
  32. Proba, K., Worn, A., Honegger, A., and Plückthun, A., 1998, Antibody scFv fragments without disulfide bonds made by molecular evolution. J. Mol. Biol. 275: 245–253PubMedCrossRefGoogle Scholar
  33. Rajpal, A., and Turi, T.G., 2001, Intracellular stability of anti-caspase-3 intrabodies determines efficacy in retargeting the antigen. J. Biol. Chem. 276: 33139–33146PubMedCrossRefGoogle Scholar
  34. Richardson, J.H., Sodroski, J.G., Waldmann, T.A., and Marasco, W.A., 1995, Phenotypic knockout of the high-affinity human interleukin 2 receptor by intracellular single-chain antibodies against the alpha sub-unit of the receptor. Proc. Natl. Acad. Sci. USA 92: 3137–3141PubMedCrossRefGoogle Scholar
  35. Segal, D.M., Weiner, G.J., Weiner, L.M., 1999, Bispecific antibodies in cancer therapy. Cur. Opinion in Immunol. 11: 558–562CrossRefGoogle Scholar
  36. Tanaka, T., and Rabbitts, T.H., 2003, Intrabodies based on intracellular capture frameworks that bind the RAS protein with high affinity and impair oncogenic transformation. EMBO J. 22: 1025–1035PubMedCrossRefGoogle Scholar
  37. Townsend, S.E., and Allison, J.P., 1993, Tumor rejection after direct co-stimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259: 368–370PubMedCrossRefGoogle Scholar
  38. Visintin, M., Tse, E., Axelson, H., Rabbitts, T.H., and Cattaneo, A., 1999, Selection of antibodies for intracellular function using a two-hybrid in vivo system. Proc. Natl. Acad. Sci. USA 9: 11723–11728CrossRefGoogle Scholar
  39. Visintin, M., Settanni, G., Maritan, A., Graziosi, S., Marks, J.D., and Cattaneo, A., 2002, The intracellular antibody capture technology (LACT): towards a consensus sequence for intracellular antibodies. J. Mol. Biol. 317: 73–83PubMedCrossRefGoogle Scholar
  40. Wang-Johanning, F., Gillespie, G.Y., Grim., J., Rancourt, C., Alvarez, R.D., Siegal, G.P., and Curiel, D.T., 1998, Intracellular expression of a single-chain antibody directed against human papillomavirus type 16 E7 oncoprotein achieves targeted antineoplastic effects. Cancer Res. 58: 1893–1900PubMedGoogle Scholar
  41. Wirtz, P., and Steipe, B., 1999, Intrabody construction and expression III: engineering hyperstable V(H) domains. Protein Sci. 8: 2245–2250PubMedCrossRefGoogle Scholar
  42. Weiner, L.M., Holmes, M., Adams, G.P., LaCreta, F., Watts, P., and Garcia de Palazzo, I., 1993, A human tumor xenograft model of therapy with a bispecific monoclonal antibody targeting c-erbB-2 and CD 16. Cancer Res. 53: 94–100PubMedGoogle Scholar
  43. Zhu, Q., Zeng, C., Huhalov, A., Yao, J., Turi, T.G., Danley, D., Hynes, T., Cong, Y., DiMattia, D., Kennedy, S., Daumy, G., Schaeffer, E., Marasco, W.A., and Huston, J.S., 1999, Extended half-life and elevated steady-state level of a single-chain Fv intrabody are critical for specific intracellular retargeting of its antigen, caspase-7. J. Immunol. Methods 231: 207–22.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  1. 1.15 rue de l’Ecole de MédecineUnité INSERM 255, Centre de Recherches Biomédicales des Cordeliers75270 Paris cedex 06France

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