Summary
By using a bispecific monoclonal antibody recognising both carcinoembryonic antigen (CEA) and the cytostatic vinca alkaloid drugs we have been able to show specific tumour localisation of vinca alkaloids. In vitro studies with sections of human colorectal tumours have demonstrated that the hybrid-hybrid 28.19.8 monoclonal is able to specifically localise vindesine to cells expressing CEA. Furthermore, the hybrid-hybrid 28.19.8 localises in vivo preferentially to tumour tissues in nude mice bearing the MAWI human xenograft tumour. This tumour-bound hybrid-hybrid monoclonal antibody induces profound changes in the bio-distribution of vinca alkaloid drugs, targeting them specifically to tumour tissues.
Similar content being viewed by others
References
Arnon R, Sela M (1982) In vitro and in vivo efficacy of conjugates of daunomycin with anti-tumour antibodies. Immunol Rev 62:5
Baldwin RW, Byers VS (eds) (1985) In: Monoclonal antibodies for cancer detection and therapy. Academic Press
Blytham H, Casellas P, Gros O, Gros P, Jansen FK, Paolucci BP, Vidal H (1981) Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells. Nature 290:145
Bumol TF, Wang QC, Reisfeld RA, Kaplan NO (1983) Monoclonal antibody and an antibody-toxin conjugate to a cell surface proteoglycan of melanoma cells suppress in vivo tumour growth. Proc Natl Acad Sci USA 80:529
Corvalan JRF, Smith W (1987) Construction and characterisation of a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids. Cancer Immunol Immunother 24:127–132
Corvalan JRF, Smith W, Gore VA, Brandon DR, Ryde P (1987) Increased therapeutic effect of vinca alkaloids targeted to tumour by a hybrid-hybrid monoclonal antibody. Cancer Immunol Immunother 24:138–143
Garnett MC, Embleton MJ, Jacobs E, Baldwin RW (1983) Preparation and properties of a drug-carrier-antibody conjugate showing selective antibody-directed cytotoxicity in vitro. Int J Cancer 31:661
Kanellos J, Pietrsz GA, McKenzie IFC (1985) Studies of methotrexate-monoclonal antibody conjugates for immunotherapy. J Natl Cancer Inst 75:319
Lewis JCM, Smith PA, Keep PA, Boxer GM (1983) A comparison of the content and immunohistochemical patterns of CEA-like activity in human colorectal tumours and nude mouse xenografts. Exp Pathol 24:227
Mason DW, Williams AF (1980) The kinetics of antibody binding to membrane antigens in solution and at the cell surface. Biochem J 187:1
Nisonoff A, Rivers MM, (1961) Recombination of a mixture of univalent antibody fragments of different specificity. Arch Biochem Biophs 93:460
Pimm MV, Armitage NC, Perkins AC, Smith W, Baldwin RW (1985) Localisation of an anti-CEA monoclonal antibody in colorectal carcinoma xenograft. Cancer Immunol Immunother 19:8
Raso V (1982) Antibody mediated delivery of toxic molecules to antigen bearing target cells. Immunol Rev 62:93
Raso V, Griffin T (1981) Hybrid antibodies with dual specificity for the delivery of ricin to immunoglobulin-bearing targets. Cancer Res 41:2073
Rowland GF, Simmonds RG, Corvalan JRF, Baldwin RW, Brown JP, Embleton MJ, Ford CH, Hellstrom KE, Hellstrom I, Kempshead JT, Newman CE, Woodhouse CS (1983) Monoclonal antibodies for targeted therapy with vindesine 30: 375
Rowland GF, Corvalan JRF, Axton CA, Gore VA, Marsden CH, Smith W, Simmonds RG (1984) Suppression of growth of a human colorectal tumour in nude mice by vindesinemonoclonal anti-CEA conjugates. Protides of the Biol Fluids 31:783
Rowland GF, Axton CA, Baldwin RW, Brown JP, Corvalan JRF, Embleton MJ, Gore VA, Hellstrom I, Hellstrom KE, Jacobs E, Marsden CH, Pimm MV, Simmonds RG, Smith W (1985) Antitumour properties of vindesine-monoclonal antibody conjugates. Cancer Immunol Immunother 19:1
Rowland GF, Simmonds RG, Gore VA, Marsden CH, Smith W (1986) Drug localisation and growth inhibition studies of vindesine-monoclonal anti-CEA conjugates in a human tumour xenograft. Cancer Immunol Immunother 21:183
Simmonds RG, Smith W, Corvalan JRF (1984) Affinity purification of anti-CEA antibody. Protides of the Biol Fluids 31:917
Thorpe PE, Brown ANF, Bremner JAG, Foxwell BMJ, Stirpe F (1985) An immunotoxin composed of monoclonal anti-Thy 1.1 antibody and a ribosome-inactivating protein from Saponaria officinalis: Potent antitumour murine effects in vitro and in vivo. J Natl Cancer Inst 75:151
Vitteta ES, Krolick KA, Miyama-Inaba M, Cushley W, Uhr JW (1983) Immunotoxins: A new approach to cancer therapy. Science 219:644
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Corvalan, J.R.F., Smith, W., Gore, V.A. et al. Specific in vitro and in vivo drug localisation to tumour cells using a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids. Cancer Immunol Immunother 24, 133–137 (1987). https://doi.org/10.1007/BF00205590
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205590