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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Dec;79(24):7896–7899. doi: 10.1073/pnas.79.24.7896

Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat alpha-fetoprotein antibodies.

Y Tsukada, E Hurwitz, R Kashi, M Sela, N Hibi, A Hara, H Hirai
PMCID: PMC347456  PMID: 6185954

Abstract

Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R., Sela M. In vitro and in vivo efficacy of conjugates of daunomycin with anti-tumor antibodies. Immunol Rev. 1982;62:5–27. doi: 10.1111/j.1600-065x.1982.tb00387.x. [DOI] [PubMed] [Google Scholar]
  2. Bernstein A., Hurwitz E., Maron R., Arnon R., Sela M., Wilchek M. Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies. J Natl Cancer Inst. 1978 Feb;60(2):379–384. doi: 10.1093/jnci/60.2.379. [DOI] [PubMed] [Google Scholar]
  3. Blythman H. E., Casellas P., Gros O., Gros P., Jansen F. K., Paolucci F., Pau B., Vidal H. Immunotoxins: hybrid molecules of monoclonal antibodies and a toxin subunit specifically kill tumour cells. Nature. 1981 Mar 12;290(5802):145–146. doi: 10.1038/290145a0. [DOI] [PubMed] [Google Scholar]
  4. Eshhar Z., Ofarim M., Waks T. Generation of hybridomas secreting murine reaginic antibodies of anti-DNP specificity. J Immunol. 1980 Feb;124(2):775–780. [PubMed] [Google Scholar]
  5. Gilliland D. G., Steplewski Z., Collier R. J., Mitchell K. F., Chang T. H., Koprowski H. 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. 1980 Aug;77(8):4539–4543. doi: 10.1073/pnas.77.8.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hurwitz E., Levy R., Maron R., Wilchek M., Arnon R., Sela M. The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Cancer Res. 1975 May;35(5):1175–1181. [PubMed] [Google Scholar]
  7. Hurwitz E., Maron R., Bernstein A., Wilchek M., Sela M., Arnon R. The effect in vivo of chemotherapeutic drug--antibody conjugates in two murine experimental tumor systems. Int J Cancer. 1978 Jun 15;21(6):747–755. doi: 10.1002/ijc.2910210612. [DOI] [PubMed] [Google Scholar]
  8. Isaka H., Umehara S., Yoshii H., Tsukada Y., Hirai H. Alpha-fetoprotein and albumin produced by subclonal cell population of the ascites hepatoma AH-66 in vitro. Gan. 1976 Feb;67(1):131–135. [PubMed] [Google Scholar]
  9. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  10. Koji T., Ishii N., Munehisa T., Kusumoto Y., Nakamura S., Tamenishi A., Hara A., Kobayashi K., Tsukada Y., Nishi S. Localization of radioiodinated antibody to alpha-fetoprotein in hepatoma transplanted in rats and a case report of alpha-fetoprotein antibody treatment of a hepatoma patient. Cancer Res. 1980 Aug;40(8 Pt 2):3013–3015. [PubMed] [Google Scholar]
  11. Krolick K. A., Uhr J. W., Vitetta E. S. Selective killing of leukaemia cells by antibody-toxin conjugates: implications for autologous bone marrow transplantation. Nature. 1982 Feb 18;295(5850):604–605. doi: 10.1038/295604a0. [DOI] [PubMed] [Google Scholar]
  12. Köhler G., Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur J Immunol. 1976 Jul;6(7):511–519. doi: 10.1002/eji.1830060713. [DOI] [PubMed] [Google Scholar]
  13. Levi-Schaffer F., Bernstein A., Meshorer A., Arnon R. Reduced toxicity of daunorubicin by conjugation to dextran. Cancer Treat Rep. 1982 Jan;66(1):107–114. [PubMed] [Google Scholar]
  14. Nishi S., Hirai H. Purification of human, dog and rabbit -fetoprotein by immunoadsorbents of sepharose coupled with anti-human -fetoprotein. Biochim Biophys Acta. 1972 Sep 29;278(2):293–298. doi: 10.1016/0005-2795(72)90234-6. [DOI] [PubMed] [Google Scholar]
  15. Nishi S. Isolation and characterization of a human fetal-alpha-globulin from the sera of fetuses and a hepatoma patient. Cancer Res. 1970 Oct;30(10):2507–2513. [PubMed] [Google Scholar]
  16. Raso V., Ritz J., Basala M., Schlossman S. F. Monoclonal antibody-ricin A chain conjugate selectively cytotoxic for cells bearing the common acute lymphoblastic leukemia antigen. Cancer Res. 1982 Feb;42(2):457–464. [PubMed] [Google Scholar]
  17. Trowbridge I. S., Domingo D. L. Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumour cells. Nature. 1981 Nov 12;294(5837):171–173. doi: 10.1038/294171a0. [DOI] [PubMed] [Google Scholar]
  18. Tsukada Y., Bischof W. K., Hibi N., Hirai H., Hurwitz E., Sela M. Effect of a conjugate of daunomycin and antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells. Proc Natl Acad Sci U S A. 1982 Jan;79(2):621–625. doi: 10.1073/pnas.79.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Uotila M., Engvall E., Ruoslahti E. Monoclonal antiodies to human alphafetoprotein. Mol Immunol. 1980 Jun;17(6):791–794. doi: 10.1016/0161-5890(80)90150-9. [DOI] [PubMed] [Google Scholar]
  20. Watabe H. Purification and chemical characterization of alpha-fetoprotein from rat and mouse. Int J Cancer. 1974 Mar 15;13(3):377–388. doi: 10.1002/ijc.2910130313. [DOI] [PubMed] [Google Scholar]

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