Antibodies and Dextran as Anti-Tumour Drug Carriers

  • Ruth Arnon
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 47)


The approach described herewith is an attempt to use antibodies directed towards tumor-associated antigens or other polymers or macromolecules, as carriers for cytotoxic anti-cancer agents in order to improve the effectiveness of cancer chemotherapy.


Free Drug Lewis Lung Carcinoma Nitrogen Mustard Antibody Activity Syngeneic Mouse 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arnon, R., 1979, Anti-tumor antibodies as carriers for anti-cancer drugs, in:“Tumor-associated antigens and their specific immune response, F. Spreafico and R. Arnon, eds., Academic Press, New York.Google Scholar
  2. Bergman, Y., and Haimovich, J., 1977, Characterization of a carcino- gen-induced murine B lymphocyte cell line of C3H/eB origin, Eur. J. Immunol. 7: 413.PubMedCrossRefGoogle Scholar
  3. Bernstein, A., Hurwitz, E., Maron, R., Arnon, R., Sela, M., and Wilchek, M., 1978, Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies, J. Natl. Cancer Inst. 60: 379.PubMedGoogle Scholar
  4. Blythman, H.E., Casellas, P., Gros, O., Gros, P., Jansen, F.K., Paolucci, F., Pau, B., and Vidal, H., 1981, Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumor cells, Nature 290: 145.PubMedCrossRefGoogle Scholar
  5. Davies, D.A.L., and O’Neil, G.J., 1973, In vivo and in vitro effects of tumor specific antibodies with chlorambucil, Br. J. Cancer 28: Suppl. I, 285.Google Scholar
  6. Davies, D.A.L. and O’Neil, G.J., 1974, Protection of mice against syngeneic lymphomata, II, Collaboration between drugs and antibodies, Br. J. Cancer 30: 305.PubMedCrossRefGoogle Scholar
  7. De-Duve, C., De Barsy, T., Poole, B., Trouet, A., Tulkens, P., and van Hoof, F., 1974, Lysosomotropic agents, Biochem. Pharmacol. 23: 2495.Google Scholar
  8. Ehrlich, P., 1906, “Collected Studies on Immunity”, Vol II,John Wiley, New York.Google Scholar
  9. Eshhar, Z., Hurwitz, E., and Hadas, E., 1980, Production of hybridomas secreting monoclonal antibodies against components of normal and malignant cells, in: “New Developments With Human and Veterinary Vaccines”, Alan R. Liss Inc., New York.Google Scholar
  10. Flechner, I., 1973, The cure and concomitant immunization of mice bearing Ehrlich ascites tumors by treatment with an antibodyalkylating agent complex, Eur. J. Cancer 9: 741.PubMedCrossRefGoogle Scholar
  11. Frei, E., 1972, Prospects for cancer chemotherapy, Cancer 30: 1656.PubMedCrossRefGoogle Scholar
  12. Ghose, T., Norvell, S.T., Guclu, A., Cameron, D., Bodurtha, A., and Mac-Donald, A.S., 1972, Immunochemotherapy of cancer with chlorambucyl carrying antibody, Br. Med. J. 3: 495.PubMedCrossRefGoogle Scholar
  13. Gillagoda, A.C., Mannuel, C., Tan, C.T.C., Wollner, V., Steinberg, S.S., and Murphy, M.L., The cardiotoxicity of adriamycin and daunomycin in children, Cancer 37: 1070.Google Scholar
  14. Gilliland, D.G., Stepelewski, Z., Collier, R.J., Mitchell, K.F., Chang, T.H., and Koprowski, H., 1981, Antibody-directed cytotoxic agents: use of monoclonal antibody to direct the action of toxin A chains to colorectal carcinoma cells, Proc. Natl. Acad. Sci. U.S.A. 77: 4539.CrossRefGoogle Scholar
  15. Gregoriadis, G., 1977, Targeting of drugs, Nature 265: 407. Gronwall, A., and Ingelman, B., 1944, Untersuchungen uber dextran and sein verhalten bei parenteraler Zufuhr, Acta Physiol. Scand, 7: 97.Google Scholar
  16. Haran-Ghera, N., and Peled, A., 1973, Thymus and bone marrow derived lymphatic leukemia in mice, Nature 241: 396.CrossRefGoogle Scholar
  17. Hurwitz, E., Maron, R., Arnon, R., and Sela, M., 1975, The covalent binding of daunomycin and adriamycin to antibodies with retention of both drug and antibody activities, Cancer Res. 35: 1175.PubMedGoogle Scholar
  18. Hurwitz, E., Maron R., Arnon, R., and Sela, M., 1976, Fab dimers of anti-tumor immunoglobulins as covalent carriers of daunomycin, Cancer Biochem. Bioyhys. 1: 197.Google Scholar
  19. Hurwitz, E., Maron, R., Arnon, R., Wilchek, M., and Sela, M., 1978a, Daunomycin-immunoglobulin conjugates, uptake and activity in vitro, Eur. J. Cancer 14: 1213.CrossRefGoogle Scholar
  20. Hurwitz, E., Maron, R., Bernstein, A., Wilchek, M., Sela, M., and Arnon, R., 1978b, The effect in vivo of chemotherapuetic drug antibody conjugates in two murine experimental tumor systems, Int. J. Cancer 21: 747.CrossRefGoogle Scholar
  21. Hurwitz, E., Schechter, B., Arnon, R., and Sela, M., 1979, Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastases, In vitro and in vivo studies with Lewis Lung Carcinoma, Int. J. Cancer 24: 461.PubMedCrossRefGoogle Scholar
  22. Hurwitz, E., Wilchek, M., and Pita, J., 1980, Soluble molecules as carriers for daunorubicin, J. Applied Biochem. 2: 25.Google Scholar
  23. Hurwitz, E., Kashi, R., and Wilchek, M., 1981, Platinum couplexed anti-tumor immunoglobulins specifically inhibit DNA synthesis of tumor cells, submitted.Google Scholar
  24. Isliker, H., Cerottini, J.C., Jaton, J.-C., and Magnenat, G., 1969, Specific and non-specific fixation of plasma proteins in tumors, in: “Chemotherapy of Cancer”, Elsevier, Amsterdam.Google Scholar
  25. Katchalski, E., and Sela, M., 1958, Synthesis and chemical properties of poly-a-amino acids, Adv. Prot. Chem. 8: 243.Google Scholar
  26. Kitao, T., and Hattori, K., 1977, Concanavalin A as a carrier of daunomycin, Nature 265: 81.PubMedCrossRefGoogle Scholar
  27. Klein, E., and Klein, G., 1964, Antigenic properties of lymphoma induced by Moloney agent, J. Natl. Cancer Inst. 32: 547.PubMedGoogle Scholar
  28. Kohler, G., and Milstein, C., 1976, Derivation of specific antibody producing tissue culture and tumor lines by cell fusion, J. Immunol. 6: 511.Google Scholar
  29. Krolick, K.A., Villemez, C., Isakson, P., Uhr, J.W., And Vitetta,E.S., 1980, Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin, Proc. Natl. Acad. Sci. USA. 77: 5419.PubMedGoogle Scholar
  30. Levi-Schaffer, F., Bernstein, A., Meshorer, A., and Arnon, R., Reduced toxicity of daunomycin by conjugation to dextran, Cancer Treatment Reports, in press.Google Scholar
  31. Levy, R., Hurwitz, R., Maron, R., Arnon, R., and Sela, M., 1975, The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies, Cancer Res. 35: 1182.PubMedGoogle Scholar
  32. Magnenat, R., Schidler, R., and Isliker, H., 1969, Transport d’agents cytostatiques par le proteines plasmatiques. III. Activite’antitumorale in vitro de conjugues cytostatiqueazoproteines, Eur. J. Cancer 5: 33.PubMedCrossRefGoogle Scholar
  33. Mathe; G., Tran, B.L., and Bernard, J., 1958, Essai sur la leucemie 1210 de la souris d’une combinaison par diazotazion d’amethopterine et de y-globulines de hamsters porteurs de cette leucemie par hetergreffe, Compt. Rend. 246: 1626.Google Scholar
  34. Molteni, E.L., and Scrollini, F., 1977, Méthode,pour prolonger l’action des medicaments par la formation de composes macromoleculaires, Eur. J. Med. Chem. 9: 618.Google Scholar
  35. Nisonoff, A., Wissler, F.C., Lippman, L.N., and Woernley, D.L., 1960, Separation of univalent fragments from bivalent rabbit antibody molecule by reduction of disulfide bonds, Arch. Biochem. Biophys. 89: 230.Google Scholar
  36. O’Bryan, R.M., Luce, J.K., Talky, R.W., Gottlieb, J.K., Baker, L.H., and Bonadonna, G., 1973, Phase II evaluation of adriamycin in human neoplasia, Cancer 32: 1.PubMedCrossRefGoogle Scholar
  37. O’Neill, G.J., 1979, The use of antibodies as drug carriers, in: “Drug Carrier in Biology and Medicine”, G. Gregoriadis, ed., Academic Press, London.Google Scholar
  38. Potter, M., and Robertson, C.L., 1960, Development of plasma-cell neoplasms in BALB/c mice after intraperitoneal injection of paraffin-oil adjuvant, heat-killed staphylococcus mixtures, J. Natl. Cancer Inst. 25: 847.PubMedGoogle Scholar
  39. Rubens, R.D., and Dulbecco, R., 1974, Augmentation of cytotoxic drug action by antibodies directed at cell surface, Nature 248: 81.PubMedCrossRefGoogle Scholar
  40. Segerling, M., Ohanian, S.H., and Borsos, T., 1974, Effect of metabolic inhibitors on killing of tumor cells by antibody and complement, J. Natl. Cancer Inst. 53: 1411.PubMedGoogle Scholar
  41. Sequira, K., and Stock, C.C., 1955, Studies in a tumor spectrum. III. The effects of phosphoramides on the growth of a variety of mouse and rat tumors, Cancer Res. 15: 38.Google Scholar
  42. Szekerke, M., Wade, R., and Whisson, M.E., 1967, Some serum protein nitrogen mustard complexes with high chemotherapeutic selectivity, Nature, 215: 1303.CrossRefGoogle Scholar
  43. Szekerke, M., Wade, R., and Whisson, M.E., 1972, The use of macromolecules as carriers of cytotoxic groups. I. Conjugates of nitrogen mustards with proteins, polypeptidyl proteins and polypeptides, Neoplasma 19: 179.Google Scholar
  44. Trouet, A., Deprez-de Campeneere, D., and De Duve, C., 1972, Chemotherapy through lysosomes with a DNA-daunorubicin complex, Nature 239: 110.CrossRefGoogle Scholar
  45. Trouet, A., Deprez-’de Campeneere, D., De Smedt-Molengreaux, M., Attasi, G., 1974, Experimental leukemia chemotherapy with a “lysosomotropic” adriamycin-DNA complex, Eur. J. Cancer 10: 405.PubMedCrossRefGoogle Scholar
  46. Varga, J.M., Asato, N., Lande, S., and Lerner, A.B., 1977, Melanotropin-daunomycin conjugate shows receptor-mediated cytotoxicity in cultured murine melanoma cells, Nature 267: 56.PubMedCrossRefGoogle Scholar
  47. Youle, R.J., and Neville, Jr., D.M., 1980, Anti-thy-1,2 monoclonal antibody linked to ricin is a potent cell type specific toxin, Proc. Natl. Acad. Sci. USA 77: 5843.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Ruth Arnon
    • 1
  1. 1.Department of Chemical ImmunologyThe Weizmann Institute of ScienceRehovotIsrael

Personalised recommendations