Ovarian Cancer pp 749-756 | Cite as

Direction of the Recognition Specificity of Cytotoxic T Cells Toward Tumor Cells by Transduced, Chimeric T-Cell Receptor Genes

  • Martina Maurer-Gebhard
  • Marc Azémar
  • Uwe Altenschmidt
  • Matjaz Humar
  • Bernd Groner
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 39)


Cellular transformation does not necessarily require the expression of proteins with neoantigenic properties, and for this reason, immunosurveillance does not register all tumor cells. They frequently express potentially immunogenic components, but are able to escape elimination by immune mechanisms. One explanation for this escape is poor antigen presentation by the tumor cells, resulting in little or no measurable antitumor immunity in immunocompetent hosts. T cells remain naive or even become anergic to the tumor cells. Reasons for the deficient antigen presentation by the tumor cells include the reduced or absent expression of major histocompatibility complex (MHC) molecules and the absence of tumor antigens in the groove of class I or class II MHC molecules as a consequence of defective protein processing. Other reasons are the absence or inadequate levels of expression of adhesion molecules, the absence or inadequate levels of costimulatory molecules or the expression of lymphocyte suppressive cytokines like transforming growth factor (TGF-β) or interleukin 10 (IL-10) by tumor cells (1-5).


Major Histocompatibility Complex Molecule Chimeric Receptor Complete DMEM Packaging Cell Line Nylon Wool 
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  1. 1.
    Refisto, N. P., Kawakami, Y., Marincola, F., Shamamiau, P., Taggarse, A., Esquivel, F., et al. (1993) Molecular mechanisms used by tumors to escape immune recognition: immunogene therapy and the cell biology of major histocompatibility complex class I. J. Immunother. 14, 182–190.CrossRefGoogle Scholar
  2. 2.
    Allison, J. P., Hurwitz, A. A., and Leach D. R. (1995) Manipulation of costimulatory signals to enhance antitumor T cell responses. Curr. Opinion Immunol. 7, 682–686.CrossRefGoogle Scholar
  3. 3.
    Guinan, E. V., Gribben, J. G., Boussiotis, V. A., Freeman G. J., and Nadler, L. M. (1994) Pivotal role of B 7: CD 28 pathway in transplantation tolerance and tumor immunity. Blood 84, 3261–3282.PubMedGoogle Scholar
  4. 4.
    Marrack, P. and Kappler, J. (1994) Subversion of the immune system by pathogens. Cell 76, 323–332.CrossRefPubMedGoogle Scholar
  5. 5.
    Moore, K. W., O’Garra, A., and de Waal Malefyt, R. (1993) Interleukin 10. Annu Rev. Immunol. 11, 165–171.CrossRefPubMedGoogle Scholar
  6. 6.
    Grimm, E. A., Muzumber, A., Zhang, H. Z., and Rosenberg, S. A. (1982) Lymphokine activated killer cell phenomenon. Lysis of natural killer resistant fresh solid tumor cells by interleukin 2 activated autologous human periferal blood lymphocytes. J. Exp. Med. 155, 1823–1841.CrossRefPubMedGoogle Scholar
  7. 7.
    Parmiani, G. (1990) An explanation of the variable clinical response to the interleukine 2 and LAK cells. Immunol. Today 11, 113–115.CrossRefPubMedGoogle Scholar
  8. 8.
    Rosenberg, S. A., Spiess, P. J., and Lafrenière, R. (1986) A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science 233, 1318–1321.CrossRefPubMedGoogle Scholar
  9. 9.
    Rosenberg, S. A., Yannelli, J. R., Yang, J. C., Topolian, S. L., Schwarzentruber, D. J., Weber, J. S., et al. (1994) Treatment of patients with metastatic melanoma with autologous tumor infiltrating lymphocytes and interleukin 2. J. Natl. Cancer Inst. 86, 1159–1166.CrossRefPubMedGoogle Scholar
  10. 10.
    Rosenberg, S. A. (1992). The immunotherapy and gene therapy of cancer. J. Clin. Oncol. 10, 180–199.PubMedGoogle Scholar
  11. 11.
    Fisher, B., Packard, B., and Read, E. (1989) Tumor localization of adoptively transfered indium 111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J. Clin. Oncol. 7, 250–261.PubMedGoogle Scholar
  12. 12.
    Waldmann, T. A. (1991) Monoclonal antibodies in diagnosis and therapy. Science 253, 1657–1662.CrossRefGoogle Scholar
  13. 13.
    Brocker, T., Peter, A., Tannecker, A., and Karjalainen, K. (1993) New simplified molecular design for functional T cell receptor. Eur. J. Immunol. 23, 1435–1439.CrossRefPubMedGoogle Scholar
  14. 14.
    Eshar, Z., Waks, T., Gross, G., and Schindler, D. J. (1993) Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the γ or ζ subunits of the immunoglobulin and T cell receptors. Proc. Natl. Acad. Sci. USA 90, 720–724.CrossRefGoogle Scholar
  15. 15.
    Moritz, D., Wels, W., Mattern, F., and Groner, B. (1994) Cytotoxic T lymphocytes with a grafted recognition specificity for erbB2 expressing tumor cells. Proc. Natl. Acad. Sci. USA 91, 4318–4322.CrossRefPubMedGoogle Scholar
  16. 16.
    Hwu, P., Schafer, G. E., Theisman, J., Schindler, D. G., Gross, G., Cowherd, R., et al. (1993) Lysis of ovarian cancer cells by human lymphocytes redirected with chimeric gene composed of antibody variable region and the Fc receptor γ chain. J. Exp. Med. 178, 361–366.CrossRefPubMedGoogle Scholar
  17. 17.
    Weijtens, M. E., Willemsen, R. A., Valerio, D., Stam, K., and Bolhuis, S. (1996) Single chain Ig/gammma gene-redirected human T lymphocytes produce cytokines, specifically lyse tumor cells and recycle lytic capacity. J. Immunol. 157, 836–843.PubMedGoogle Scholar
  18. 18.
    Morgenstern, J. P. and Land, H. (1990) A series of mammalianexpression vectors and characterization of a reporter gene in stably and transiently transfected cells. Nucleic Acid Res. 18, 3587–3596.CrossRefPubMedGoogle Scholar
  19. 19.
    Moritz, D., et al. (1994) Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2expressing tumor cells. Proc. Natl. Acad. Sci. USA 91, 4318–322.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  • Martina Maurer-Gebhard
    • 1
  • Marc Azémar
    • 1
  • Uwe Altenschmidt
    • 1
  • Matjaz Humar
    • 1
  • Bernd Groner
    • 2
  1. 1.Institute for Experimental Cancer ResearchTumor Biology CenterFreiburgGermany
  2. 2.Chemotherapeutisches ForschungsinstitutGeorg Speyer HausFrankfurtGermany

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