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Mechanism of Rapid Tumor Lysis by Human ADCC: Mediation by Monoclonal Antibodies and Fragmentation of Target Cell DNA

  • Duane W. Sears
  • Jeffrey E. Christiaansen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 187)

Abstract

Immunologically programmed cell destruction is an important defense mechanism for limiting the spread of invasive intracellular parasites and malignant cells in the body (1,2). However, when such processes are misdirected, in autoimmune diseases for example, they can be very harmful to normal tissues and can interfere with vital tissue functions (2). Thus, it is of considerable value to understand the mechanisms of cytolytically induced cell destruction as mediated by the immune system. Several such mechanisms have evolved with the immune system of man, and each is characterized by distinct antigen recognition requirements and/or distinct lytic processes. Some cytolytic mechanisms require only the secreted products of cells and not the direct intervention of an effector cell for cytolysis to occur, as with complement plus antibody-mediated cytotoxicity (CAMC), for example. Other mechanisms, however, do require that intimate contact be made between an effector cell and its target cell. Various lymphocytes, such as cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and killer (K) cells all appear to initiate the lytic process only after contact is made with the target cell (1–4).

Keywords

Natural Killer Target Cell Effector Cell K562 Cell Mixed Lymphocyte Culture 
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.

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References

  1. 1.
    Perlman, P. and J.-C. Cerottini. 1979. Cytotoxic Lymphocytes. The Antigens. M. Sela, editor. Academic Press, Inc. New York. 173–281.Google Scholar
  2. 2.
    Pearson, G.R. 1978. In vitro and in vivo investigations on antibody-dependent cellular cytotoxicity. Curr. Top. Microbiol. Immunol. 80:65.CrossRefGoogle Scholar
  3. 3.
    Henney, C.S. 1977. T-cel1-mediated cytolysis: an overview of some current issues. Contemp. Top. Immunobiol. 7:245.CrossRefGoogle Scholar
  4. 4.
    Wright, S.C. and B. Bonavida. 1982. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). 1. Release of cytotoxic factors specific for NK sensitive target cells (NKCF) during coculture of NK effector cells with NK target cells. Immunol. 129:433.Google Scholar
  5. 5.
    Sissons, J.G.P. and M.A. Oldstone. 1980. Antibody-mediated destruction of virus-infected cells. Adv. Immunol. 29:209.PubMedCrossRefGoogle Scholar
  6. 6.
    Christiaansen, J.E. and D.W. Sears. 1984. Unusually efficient tumor cell lysis by human effectors of ADCC mediated by monoclonal antibodies. Cancer Res. In press.Google Scholar
  7. 7.
    Pious, D., P. Hawley, and G. Forrest. 1973. Isolation and characterization of HLA-variants in cultured human lymphoid cells. Proc. Natl. Acad. Sci. 70:1397.PubMedCrossRefGoogle Scholar
  8. 8.
    Christiaansen, J.E., D. Gallardo, S.S. Burnside, A.A. Nelson, and D.W. Sears. 1984. Rapid covalent coupling of proteins to cell surfaces: Immunological characterization of viable protein-cell conjugates. Submitted for publication.Google Scholar
  9. 9.
    Russell, J.H. and C.B. Dobos. 1980. Mechanism of immune lysis. II. CTL-induced nuclear disintegration of the target begins within minutes of cell contact. J. Immunol. 225:1256.Google Scholar
  10. 10.
    Duke, R.C., R. Chervenak, and J.J. Cohen. 1983. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc. Natl. Acad. Sci. 80:6361.PubMedCrossRefGoogle Scholar
  11. 11.
    Russell, J.H., V.R. Masakowski, and C.B. Dobos. 1980. Mechanism of immune lysis. 1. Physiological distinction between target cell death-mediated by cytotoxic T lymphocytes and antibody plus complement. J. Immunol. 124:1100.PubMedGoogle Scholar
  12. 12.
    Karen, H.S. and P.J. Jensen. 1980. Natural killing and antibody-dependent cellular cytotoxicity: independent mechanisms mediated by overlapping cell populations, in Natural Cell-Mediated Immunity Against Tumors. R.B. Herberman, editor. Academic Pres, Inc. New York. 347–363.Google Scholar
  13. 13.
    de Landazuri, M.O., A. Silva, J. Alvarez, and R.B. Herberman. 1979. Evidence that natural cytotoxicity and antibody- dependent cellular cytotoxicity are mediated in humans by the same effector cell populations. J. Immunol. 123:252.PubMedGoogle Scholar
  14. 14.
    Perussia, B., S. Starr, S. Abraham, V. Fanning, and G. Trinchieri. 1983. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J. Immunol. 130:2142.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Duane W. Sears
    • 1
  • Jeffrey E. Christiaansen
    • 1
  1. 1.Department of Biological SciencesUniversity of California, Santa BarbaraSanta BarbaraUSA

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