Selective Cytotoxicity of Ricin a Chain-Anti Carcinoembryonic Antibody Conjugates to Human Adenocarcinoma Cells

  • Thomas W. Griffin
  • Linda R. Haynes
  • Larissa V. Levin


Studies of immunotoxins as selective anti-tumor agents have been performed primarily with hematologic tumor antigens, such as mouse T cell differentiation antigens (1, 2) and immunoglobulin on the surface of murine and human B cell leukemia cells (3–6). We have recently explored this approach utilizing antibodies directed against the carcinoembryonic antigen, CEA (7–9), a well described tumor-associated antigen of adult human solid malignancies.


Carcinoembryonic Antigen LoVo Cell Leucine Incorporation Selective Cytotoxicity WiDr Cell 


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  1. 1.
    F.K. Jansen, H.E. Blythman, D. Carrière, P. Casellas, J. Diaz, P. Gros, J.R. Hennequi, S. Paolucci, B. Pau and P. Poncelet. High specific cytotoxicity of antibody-toxin hybrid molecules (immunotoxins) for target cells, Immunol. Lett. 2:97 (1980).CrossRefGoogle Scholar
  2. 2.
    R.J. Youle and D.M. Neville. Anti-thy 1,2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin, Proc. Natl. Acad. Sci. USA. 77:4883 (1980).CrossRefGoogle Scholar
  3. 3.
    V. Raso and T. W. Griffin. Specific cytotoxicity of a human immunoglobulin directed Fab’-ricin A chain conjugate, J. Immunol. 125:2610 (1980).PubMedGoogle Scholar
  4. 4.
    V. Raso and T.W. Griffin. Hybrid antibodies with dual specificity for the delivery of ricin to immunoglobulin-bearing target cells, Cancer Res. 41:2073 (1981).PubMedGoogle Scholar
  5. 5.
    K.A. Krolick, C. Villemez, P. Isakson, J.W. Uhr and E.S. Vitetta. Selective killing of normal and neoplastic B cells by antibodies coupled to the A chain of ricin, Proc. Natl. Acad. Sci. USA. 77:5419 (1980).PubMedCrossRefGoogle Scholar
  6. 6.
    K.A. Krolick, J.W. Uhr, S. Slavid and E. S. Vitetta. In-vivo therapy of a murine B cell tumor (BCL) using antibody-ricin A chain immunotoxins, J. Exp. Med. 155:1797 (1982).PubMedCrossRefGoogle Scholar
  7. 7.
    T.W. Griffin, L.R. Haynes and J. A. DeMartino. Selective cytotoxicity of a ricin A chain anti-CEA antibody conjugate for a human colonic adenocarcinoma cell line, J. Natl. Cancer Inst. 69:799 (1982).PubMedGoogle Scholar
  8. 8.
    L.V. Levin, T.W. Griffin, L.R. Haynes and C. J. Sedor. Selective cytotoxicity for a colorectal carcinoma cell line by a monoclonal anticarcinoembryonic antigen antibody coupled to the A chain of ricin, J. Biol. Resp. Modif. 1:149 (1982).Google Scholar
  9. 9.
    L.V. Levin, T.W. Griffin, L.R. Haynes and D. Haagenson. Conjugates of antibody directed against CEA disulfide linked to ricin A chain demonstrate selective cytotoxicity to human CEA bearing cells in culture, Proc. Am. Ass. Cancer Res. 24: 222 (1983).Google Scholar
  10. 10.
    P. Gold and S. O. Freedman. Demonstration of tumor specific antigens in human colonic carcinomas by immunological tolerance and absorption technique, J. Exp. Med. 122:439 (1965).CrossRefGoogle Scholar
  11. 11.
    C.H.J. Ford, C.E. Newman, J.R. Johnson, C.S. Woodhouse, T.A. Reeder, G.F. Rowland and R.G. Simmonds. Localization and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer, Br. J. Cancer 47:35 (1983).PubMedCrossRefGoogle Scholar
  12. 12.
    J.P. Mach, F. Buchegger, M. Forni, J. Ritschard, C. Berche, J.D. Lumbruso, M. Schreger, C. Giradet, R.S. Accolla and S. Carrel. Use of radiolabeled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photo-scanning and tomoscintography, Immunol. Today 2:239 (1981).CrossRefGoogle Scholar
  13. 13.
    D. M. Goldenberg, F. Leland, E. Kim, S. Bennett, F. J. Primus, J. R. van Nagell, N. Estes, P. DeSimone and P. Rayburn. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localisation of diverse cancers by external photoscanning, N. Engl. J. Med. 298:1384 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    E. Alpert. The immunochemical complexity of CEA. A golden dream or molecular nightmare, Cancer 42:1585 (1978).PubMedCrossRefGoogle Scholar
  15. 15.
    D. J. Hnatowich, W. W. Layne, R. L. Childs, D. Lanteigne, M. A. Davis, T. W. Griffin and P. W. Doherty. Radiolabeling antibody: a simple and efficient method, Science 222:613 (1983).CrossRefGoogle Scholar
  16. D. E. Haagensen, M. S. Huberman, A. Kaldany, S. Davis, K. George and C. Moore. Phase I–II immunotherapy trial of non-human primate (baboon) anti-CEA antibody for treatment of metastatic adenocarcinoma which secretes CEA, Proc. Am. Ass. Cancer Res. 24:209 (1983).Google Scholar
  17. 17.
    R. J. Youle and D. M. Neville. Kinetics of protein synthesis inactivation by ricin-anti-thy 1.1 monoclonal antibody hybrids, J. Biol. Chem. 257:1598 (1982).PubMedGoogle Scholar
  18. 18.
    P. Cassellas, J.P. Brown, O. Gros, P. Gros, I. Hellstrom, F.K. Jansen, P. Poncelet, R. Roncucci, H. Vidal and K.E. Hellstrom. Human melanoma cells can be killed in-vitro by an immunotoxin specific for melanoma-associated antigen, Int. J. Cancer 30:437 (1982).CrossRefGoogle Scholar
  19. 19.
    D.J R. Fitzgerald, R. Padmanabran, I. Pastan and M.C. Willingham. Adenovirus-induced release of epidermal growth factor and Pseudomonas toxin into the cytosol of B cells during receptor-mediated endocytosis, Cell 32:607 (1983).PubMedCrossRefGoogle Scholar
  20. 20.
    K.S. Webb, J.L. Ware, S.E. Parks, W.H. Briner and P. Paulson. Monoclonal antibodies to different epitopes on a prostate tumor-associated antigen, Cancer Immunol. Ther. 14:155 (1983).Google Scholar
  21. 21.
    I. Hellstrom, J.P. Brown and K. E. Hellstrom. Monoclonal antibodies to two determinants of melanoma-antigen 97 act synergist ically in complement-dependent cytotoxicity, J. Immunol. 127:159 (1981).Google Scholar
  22. 22.
    H. Sands, P.L. Jones, W. Neacy, L. Canin and B. M. Gallagher. A comparison of the ability of radio-iodinated monoclonal anti-rat Thy 1 (0x7) to image SL2 tumors located subcut-aneously or in the subrenal capsule, Proc. 30th Ann. Meeting Soc. Nucl. Med. J. Nucl. Med. 24:102 (1983).Google Scholar
  23. 23.
    A.E. Bogden, D.J. Hnatowich, P.W. Doherty and T.W. Griffin. In-vivo localization of monoclonal antibody in fresh surgical expiants of human tumors: 3 day subrenal capsule assay, Proc. Am. Ass. Cancer Res. 24:218 (1983).Google Scholar
  24. 24.
    D.G. Gilliland, P. Stephenski, R.J. Collier, K.E. Mitchell, T.H. Chang and H. Koprowski. Antibody directed cytotoxic agents: use of monoclonal antibody to direct the action of toxic A chains to colorectal carcinoma cells, Proc. Natl. Acad. Sci. USA. 77:4539 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    K.A. Krolick, D. Yuan and E. S. Vitetta. Specific killing of a breast carcinoma cell line by a monoclonal antibody coupled to the A chain of ricin, Cancer Immunol. Immunotherapy 12:39 (1981).CrossRefGoogle Scholar
  26. 26.
    K.L. Rosenthal, W.A.F. Tompkins and W.E. Rawls. Factors affecting the expression of carcinoembryonic antigen at the surface of cultured human colon carcinoma cells, Cancer Res., 40:4744 (1980).PubMedGoogle Scholar
  27. 27.
    D.M. Goldenberg, R.M. Sharkey and F.F. Primas. Immunocyto-chemical detection of carcinoembryonic antigen in conventional histopathology specimens, Cancer 42:1546 (1978).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Thomas W. Griffin
    • 1
  • Linda R. Haynes
    • 1
  • Larissa V. Levin
    • 1
  1. 1.Division of Oncology, Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

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