Abstract
The idea that antibodies directed against tumor-associated antigens might be used to target a toxic agent specifically to tumor cells and so spare normal tissue from harm has attracted much attention recently. This is mainly because the advent of hybridoma technology for making monoclonal antibodies overcame the problems inherent in using conventionally raised polyclonal antibodies and made this approach much more feasible. Toxins of plant (e.g. ricin, abrin and gelonin) or bacterial (e.g. diphtheria toxin, pseudomonas aeruginosa exotoxin A) origin have proved particularly promising for targeting purposes, probably because their extreme potency minimises the number of toxin molecules that have to be delivered to a target cell to kill it. Antibody-toxin conjugates (‘immunotoxins’) have in many in vitro and in vivo experimental systems been found to kill cancer cells with great potency and specificity.
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References
Blakey, D. C, and Thorpe, P. E., 1986, Effect of chemical deglycosylation on the in vivo fate of ricin A-chain, Cancer Drug Delivery, 3:189.
Blakey, D. C, Wawrzynczak, E. J., Wallace, P. M., and Thorpe, P. E., 1987a, Antibody toxin conjugates: a perspective in: “Progress in Allergy,” H. Waldmann, ed., S. Karger AG., Basel, in press.
Blakey, D. C., Wawrzynczak, E. J., Stirpe, F., and Thorpe, P. E., 1987b, Anti-tumor activity of a panel of anti-Thy 1.1 immunotoxins made with different ribosome inactivating proteins in: “UCLA Proceedings Volume: Membrane Mediated Cytotoxicity,” B. Benjamin and R. J. Collier eds., Alan R. Liss, Inc., New York.
Blakey, D. C, Watson, G. J., Knowles, P. P., and Thorpe, P. E., 1987c, Effect of chemical deglycosylation of ricin A-chain on the in vivo fate and cytotoxic activity of an immunotoxin composed of ricin A-chain and anti-Thy 1.1. antibody, Cancer Res., 47:947.
Bourrie, B. J. P., Casellas, P., Blythman, H. E., and Jansen, F. K., 1986, Study of the plasma clearance of antibody-ricin A-chain immunotoxins. Evidence for specific recognition sites on the A-chain that mediate rapid clearance of the immunotoxins, Eur. J.Biochem., 155:1.
Byers, V., Kernan, N., Henslee, J., Gingrich, R., Frame, J. Waid, J., Messino, M., Blazer, B., Mischak, R., O’Reilly, R., Thompson, J., Dupont, B., and Scannon, P., 1987, A phase 1 study using pan T lymphocyte-ricin A chain immunotoxin to treat graft versus host disease in: “Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer,” I. Royston, R.O. Dillman eds., USCD Cancer Center, San Diego, in press.
Casellas, P., Bourrie, B. J. P., Gros, P., and Jansen, F. K., 1984, Kinetics of cytotoxicity induced by immunotoxins: enhancement by lysosomotrophic amines and carboxylic ionophores, J.Biol.Chem.,259:9359.
Eiklid, K., Olsnes, S., and Pihl, A., 1980, Entry of lethal doses of abrin, ricin and modeccin into the cytosol of HeLa cells, Exp.Cell Res., 126:321.
Filipovich, A. H., Vallera, D. A., Youle, R. J., Neville, D. M., and Kersey, J. H., 1985, Ex vivo T-cell depletion with immunotoxins in allogeneic bone marrow transplantation: the pilot clinical study for prevention of graft-versus-host disease, Transpl.Proc., 17:442.
Gorin, N. C, Douay, L., Laporte, J. P., Lopez, M., Zittoun, R., Rio, B., David, R., Stachwiak, J., Jansen, J., Cazellas, P., Poncelet, P., Liance, M. C, Voisin, G. A., Salmon, C, Le Blanc, G., Deloux, J., Najman, A., and Duhamel, G., 1985, Autologous bone marrow transplantation with marrow decontaminated by immunotoxin T101 in the treatment of leukemia and lymphoma: first clinical observations, Cancer Treat. Rep., 69:953.
Jansen, F. K., Blythman, H. E., Bourrie, B., Carriere, D., Casellas, P., Dussossoy, D., Gros, O., Laurent, J. C, Liance, M. C., Poncelet, P., Richer, G., and Vidal, H., 1984, Significance of the kinetics of immunotoxin cytotoxicity in: “Receptor Mediated Targeting of Drugs,” G. Gregoriadis, G. Poste, J. Senior and A. Trouet, eds., Plenum Press, New York.
Kishida, K., Masuho, Y., Saito, M., Hara, T., and Fuji, H., 1983, Ricin A-chain conjugated with monoclonal anti-L1210 antibody. In vitro and in vivo antitumor activity, Cancer Immunol.Immunother., 16:93.
Knowles, P. P., and Thorpe, P. E., 1987, Purification of immunotoxins containing ricin A-chain and abrin A-chain using Blue Sepharose CI 6B, Anal.Biochem., 160:440.
Laurent, G., Kuhlein, E., Casellas, P., Canat, X., Carayon, P., Poncelet, P., Correll, S., Rigal, F., and Jansen, F. K., 1986a, Determination of sensitivity of fresh leukemia cells to immunotoxins, Cancer Res., 46:2289.
Laurent, G., Pris, J., Farcet, J. P., Crayon, P., Blythman, H., Casellas, P., Poncelet, P., and Jansen, F. K., 1986b, Effect of therapy with T101 ricin A-chain immunotoxin in two leukemia patients, Blood, 67:1680.
Mcintosh, D. P., Edwards, D. C, Cumber, A. J., Parnell, G. D., Dean, C. J., Ross, W. C. J., and Forrester, J. A., 1983, ricin B-chain converts a non-cytotoxic antibody-ricin A chain conjugate into a potent and specific cytotoxic agent. FEBS Lett., 164:17.
Nolan, R. D., Grasmuk, H., and Drews, J., 1976, The binding of tritiated elongation factor 1 and 2 to the ribosomes from Krebs II mouse ascites cells. The influence of various antibiotics and toxins, Eur. J. Biochem., 64:69.
Seto, M., Umemoto, N., Saito, M., Masuho, Y., Hara, T., and Takahashi, T., 1982, Monoclonal anti-MM46 antibody:ricin A chain conjugate: In vitro and in vivo antitumor activity, Cancer Res., 42:5209.
Skilleter, D. N., and Foxwell, B. M. J., 1986, Selective uptake of ricin A-chain by hepatic non-parenchymal cells in vitro. Importance of mannose oligosaccharides in the toxin, FEBS Lett., 196:344.
Spitler, L. E., del Rio, M., Khentigan, A., Wedel, N. I., Brophy, N. A., Miller, L. L., Harkonen, W. S., Rosendorf, L. L., Lee, H. M., Mischak, R. P., Kawahata, R. T., Stoudemire, J. B., Fradkin, L. B., Bautista, E. E., and Scannon, P. J., 1987, Therapy of patients with malignant melanoma using a monoclonal anti-melanoma antibody-ricin A-chain immunotoxin, Cancer Res., 47:1717.
Thorpe, P. E., 1985, Antibody carriers of cytotoxic agents in cancer therapy in: “Monoclonal Antibodies’ 84, Biological and Clinical Applications,” A. Pinchera, G. Doria, F. Dammacco and A. Bargellesi, eds., Edritice Kurtis s.r. 1., Milan.
Thorpe, P. E., Mason, D. W., Brown, A. N. F., Simmonds, S. J., Ross, W. C. J., Cumber, A. J., and Forrester, J. A., 1982, Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate, Nature, 297:594.
Thorpe, P. E., Ross, W. C. J., Brown, A. N. F., Myers, C. D., Cumber, A. J., Foxwell, B. M. J., and Forrester, J. A., 1984, Blockade of the galactose-binding sites of ricin by its linkage to antibody: specific cytotoxic effects of the conjugate, Eur. J.Biochem., 140:63.
Thorpe, P. E., Detre, S. I., Foxwell, B. M. J., Brown, A. N. F., Skilleter, D. N., Wilson, G., Forrester, J. A., and Stirpe, F., 1985, Modification of the carbohydrate in ricin with metaperiodate-cyanoborohydride mixtures. Effects on toxicity and in vivo distribution, Eur. J.Biochem., 147:197.
Vitetta, E. S., and Uhr, J. W., 1985, Immunotoxins, Ann.Rev.Immunol., 3:197.
Vitetta, E. S., Fulton, R. J., and Uhr, J. W., 1984, Cytotoxicity of cellreactive immunotoxin containing ricin A chain is potentiated by an anti-immunotoxin containing ricin B chain, J.Exp.Med., 160:341.
Wawrzynczak, E. J., and Thorpe, P. E., 1987, Methods for preparing immunotoxins: effects of the linkage on activity and stability in: “Immunoconjugates: Antibody Conjugates in Radioimaging and Therapy of Cancer,” C.W. Vogel, ed, Oxford University Press, New York, in press.
Woodruff, M. F. A., 1983, Cellular heterogeneity in tumors, Br.J.Cancer., 47:589.
Worrell, N. R., Cumber, A. J., Parnell, G. D. Ross, W. C. J., and Forrester, J. A., 1986, Fate of an antibody-ricin A-chain conjugate administered to normal rates, Biochem.Pharmacol., 35:417.
Youle, R, J,, and Neville, D. M., 1980, Anti-Thyl.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin, Proc. Natl. Acad. Sci.USA., 77:5483.
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Blakey, D.C., Thorpe, P.E. (1988). Anti-tumor Effects of Monoclonal Antibody-ricin Conjugates In Vitro and In Vivo. In: Hubbard, R., Marks, V. (eds) Clinical Applications of Monoclonal Antibodies. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1573-5_21
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DOI: https://doi.org/10.1007/978-1-4613-1573-5_21
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