Abstract
Monoclonal antibodies (MAbs) recognizing tumor-associated antigens (TAA) have been widely used to selectively deliver toxic compounds to neoplastic cells. In most studies, tumor targeting was achieved by the use of immunotoxins (IT) generated by chemical conjugation of an antibody to a toxin (1). In addition, several recombinant antibody-toxin chimeric molecules have been generated by genetic engineering (2). Ricin A-chain, which enzymatically damages ribosomal RNA, has been most commonly used for the generation of ITs, although several other single-chain ribosome-inactivating proteins (RIPs) or type I RIPs are also available (3). Type I RIPs are RNA N-glycosidases displaying potent inhibition of protein synthesis in cell-free assays, but they lack a lectin B-chain for cell entry, and thus have a low toxicity for whole cells. Type I RIPs such as saporin can be easily purified (4) and have been successfully used to generate potent ITs, displaying antitumor activity both in vitro (5) and in vivo (6).
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References
Thrush, G. R., Lark, L. R., Clinchy, B. C., and Vitetta, E. S. (1996) Immunotoxins: an update. Annu. Rev. Immunol. 14, 49–71.
Reiter, Y. and Pastan, I. (1996) Antibody engineering of recombinant Fv immunotoxins for improved tageting of cancer: disulphide-stabilized Fv immunotoxins. Clin. Cancer Res. 2, 245–252.
Barbieri, L., Battelli, M. G., and Stirpe, F. (1993) Ribosome-inactivating proteins from plants. Biochim. Biophys. Acta 1154, 237–282.
Barbieri, L., Stoppa, C., and Bolognesi, A. (1987) Large scale chromatographic purification of ribosome-inactivating proteins. J. Chromatogr. 408, 235–243.
Bolognesi, A., Tazzari, P. L., Tassi, C., Gromo, G., Gobbi, M., and Stirpe, F. (1992) A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies. Clin. Exp. Immunol. 89, 341–346.
Pasqualucci, L., Wasik, M., Teicher, B., Flenghi, L., Bolognesi, A., Stirpe, F., et al. (1995) Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in severe combined immunodeficiency disease mice xenografted with human CD30+ anaplastic large cell lymphoma. Blood 85, 2139–2146.
Suresh, M., Cuello, A., and Milstein, C. (1986) Bispecific monoclonal antibodies from hybrid hybridomas. Methods Enzymol. 121, 210–228.
LeDoussal, J-M., Barbet, J., and Delaage, M. (1992) Bispecific monoclonal antibody-mediated targeting of radiolabeled bivalent haptens: theoretical, experimental and clinical results. Int. J. Cancer Suppl. 7, 58–62.
French, R. R., Courtenay, A. E., Ingamells, S., Stevenson, G. T., and Glennie, M. J. (1991). Cooperative mixtures of bispecific F(ab’) antibodies for delivering saporin to lymphoma in vitro and in vivo. Cancer Res. 51, 2353–2361.
Ferrini, S., Cambiaggi, A., Cantoni, C., Canevari, S., Mezzanzanica, D., Colnaghi, M. I., et al. (1992). Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies: role of different triggereing molecules. Int. J. Cancer (Suppl.) 7, 15–18.
Tazzari, P. L., Zhang, S., Chen, Q., Sforzini, S., Bolognesi, A., Stirpe, F., et al. (1993) Targeting of saporin to CD25-positive normal and neoplastic lymphocytes by an anti-saporin/anti-CD25 bispecific monoclonal antibody: in vitro evaluation. Br. J. Cancer 67, 1248–1253.
Sforzini, S., DeTotero, D., Gaggero, A., Ippoliti, R., Glennie, M. J., Canevari, S., et al. (1998) Targeting of saporin to Hodgkin’s lymphoma cells by anti-CD30 and anti-CD25 bispecific antibodies. Br. J. Haematol. 102, 1061–1062.
Engert, A., Diehl, V., Schnell, R., Radszuhun, A., Hatwig, M., Drillich, S., et al. (1997) A phase-I study of an anti-CD25 ricinA-chain immunotoxin (RFT5-SMPTdgA) in patients with refractory Hodgkin’s lymphoma. Blood 2, 403–410.
Stein, H., Mason, D. Y., Gerdes, J., O’Connor, N., Wainscoat, J., Pallesen,G., et al. (1985) The expression of the Hodgkin’s disease-associated antigen Ki-1 in reactive and neoplastic tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66, 848–858.
Falini, B., Bolognesi, A., Flenghi, L., Tazzari, P. L., Broe, M. K., Stein, H., et al. (1992) Response of refractory Hodgkin’s disease to therapy with anti-CD30 monoclonal antibody linked to saporin (BER-H2/SO6) immunotoxin. Lancet 339, 1195–1196.
French, R. R., Penney, C. A., Browning, A. C., Stirpe, F., George, A. J. T., and Glennie, M.J. (1995). Delivery of the ribosome-inactivating protein, gelonin, to lymphoma cells via CD22 and CD38 using bispecific antibodies. Br. J. Cancer 71, 986–994.
Bonardi, M. A., French, R. R., Amlot, P., Gromo, G., Modena, D., and Glennie, M.J. (1993) Delivery of saporin to human B cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37 or immunoglobulin results in efficient killing. Cancer Res. 53, 3015–3021.
Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.
Harlow, E. and Lane, D. (1988) Antibodies a Laboratory Manual. Cold Spring Harbor Laboratory, New York.
Casalini, P., Mezzanzanica, D., Canevari, S., Della Torre, G., Miotti, S., Colnaghi, M. I., et al. (1991) Use of combination of monoclonal antibodies directed against three distinct epitopes of a tumor-associated antigen: analysis of cell binding and internalization. Int. J. Cancer 48, 284–290.
Clark, M. R. and Waldmann, H. (1987) T-cell killing of target cells induced by hybrid antibodies: comparison of two bispecific monoclonal antibodies. J. Natl. Cancer Inst. 79, 1393–1401.
Glennie, M. J., McBride, H. M., Worth, A. T., and Stevenson, G. T. (1987) Preparation and performance of bispecific F(ab′)2 antibody containing thioether-linked Fab’ Fragments. J. Immunol. 139, 2367–2375.
Riechmann, L., Clark, M., Waldmann, H., and Winter, G. (1988) Reshaping human antibodies for therapy. 332, 323–327.
Nissim, A., Hoogenboom, H. R., Tomlinson, I. M., Flynn, G., Midgley, C., Lane, D., et al. (1994) Antibody fragments from a “single pot” phage display library as immunochemical reagents. EMBO J. 13, 692–698.
Mack, M., RiethmÄller, G., and Kufer, P. (1995) A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc. Natl. Acad. Sci. USA 92, 7021–7025.
Holliger, P., Prospero, T., and Winter, G. (1993) “Diabodies”: Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA 90, 6444–6448.
Tazzari, P. L., Bolognesi, A., DeTotero, D., Falini, B., Lemoli, R. M., Soria, M. R., et al. (1992) Ber-H2 (anti-CD30)-saporin immunotoxin: a new tool for the treatment of Hodgkin’s disease and CD30+ lymphoma: in vitro evaluation. Br. J. Haematol. 81, 203–211.
Fanger, M. W., Shen, L., Graziano, R. F., and Guyre, P. M. (1989) Cytotoxicity mediated by human Fc receptors for IgG. Immunol. Today 10, 92–99.
Parham, P. (1983) On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from balb/c mice. J. Immunol. 131, 2895–2902.
Warnaar, S. O., DePaus, V., Lardenoije, R., Machielse, B.N. M., DeGraaf, J., Bregonje, M., et al. (1994) Purification of bispecific F(ab′)2 from murine trinoma OC/TR with specificity for CD3 and ovarian cancer. Hybridoma, 13, 519–526.
Roosnek, E. and Lanzavecchia, A. (1989) Triggering T cells by otherwise inert hybrid anti-CD3/anti-tumor antibodies requires encounter with the specific target cell. J. Exp. Med. 170, 297–302.
Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.
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Ferrini, S., Sforzini, S., Canevari, S. (2001). Bispecific Monoclonal Antibodies for the Targeting of Type I Ribosome-Inactivating Proteins Against Hematological Malignancies. In: Hall, W.A. (eds) Immunotoxin Methods and Protocols. Methods in Molecular Biology™, vol 166. Humana Press. https://doi.org/10.1385/1-59259-114-0:177
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DOI: https://doi.org/10.1385/1-59259-114-0:177
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