Hybrid Cell Vaccination in Patients With Metastatic Melanoma

  • Uwe Trefzer
  • Guido Weingart
  • Wolfram Sterry
  • Peter Walden
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 35)


Hybrid cell vaccination is a novel approach for immunotherapy of cancers by inducing specific antitumor immunity (1 ,2). The hybrid cells are generated by electrofusing autologous tumor cells with allogeneic MHC class II expressing cells such as B lymphocytes. The fused cells are irradiated and injected subcutaneously as a vaccine. This immune therapeutical approach aims at recruitment of T-cell help for the induction of tumor-specific cytolytic immunity. It is based on the observation that epitope linkage is a prerequisite for productive T-T cell collaboration, i.e., cytolytic precursor and helper T cells have to be activated by the same antigen presenting cell that displays epitopes for both T-cell types on the corresponding MHC class I and class II molecules (3 ,4). Neither of the two epitopes nor the corresponding T cells need to be related. The implications of this concept are, first, only MHC class I and II expressing cells can induce cytolytic T-cell responses (5 -7), second, cognate antigens must be presented for both T-cell and MHC types (4 ,8) and, third, there must be T cells with the corresponding specificities in the T-cell receptor repertoire of the response-competent individual.


Hybrid Cell Glucose Solution Autologous Tumor Cell Fusion Efficiency Autologous Melanoma Cell 
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  1. 1.
    Stuhler, G. and Walden, P. (1994) Recruitment of helper T-cells for induction of tumour rejection by cytolytic T lymphocytes. Cancer Immunol. Immunother. 39, 342–345.PubMedCrossRefGoogle Scholar
  2. 2.
    Guo, Y., Wu, M., Chen, H., Wang, X., Liu, G., Li, G., et al. (1994) Effective tumour vaccine generated by fusion of hepatoma cells with activated B cells. Science 263, 518–520.PubMedCrossRefGoogle Scholar
  3. 3.
    Mitchison, N. A., Rajewski, K., and Taylor, R. B. (1970) Cooperation of antigenic determinants of cells in the induction of antibodies, in Developmental Aspects of Antibody Formation and Structure (Sterzl, J. and Riha, I., eds.), Academic, New York, pp. 547–547.Google Scholar
  4. 4.
    Mitchison, N. A. and O’Malley, C. (1987) Three-cell-type clusters of T cells with antigen-presenting cells best explain the epitope linkage and noncognate requirements of the in-vivo cytolytic response. Eur. J. Immunol. 17, 1479–1483.Google Scholar
  5. 5.
    Borges, E., Wiesmüller, K. H., Jung, G., and Walden, P. (1994) Efficacy of synthetic vaccines in the induction of cytotoxic T lymphocyte responses. J. Immunol. Meth. 173, 253–263.CrossRefGoogle Scholar
  6. 6.
    Stuhler, G. and Walden, P. (1993) Collaboration of helper and cytotoxic T lymphocytes. Eur. J. Immunol. 23, 2279–2286.PubMedCrossRefGoogle Scholar
  7. 7.
    Grabbe, S., Beissert, S., Schwarz, T., and Granstein, R. (1995) Dendritic cells as initiators of tumour immune responses: a possible strategy for tumour immunotherapy? Immunol. Today 16, 117–121.PubMedCrossRefGoogle Scholar
  8. 8.
    Mitchison, N. A. (1990) An exact comparison between the efficiency of two-and three-cell-type clusters mediating helper activity. Eur. J. Immunol. 20, 699–702.PubMedCrossRefGoogle Scholar
  9. 9.
    Trefzer, U., Weingart, G., Chen, Y., Adrian, K., Audring, H., Winter, H., et al. (1998) A phase I trial with a hybrid cell vaccine in patients with metastatic melanoma, in Proc. 3rd Europ. Conf. Gene Ther. 1997 (P. Walden, U. Trefzer, W. Sterry, and Farzaneh, F., eds.), Plenum, London, pp. 519–525.Google Scholar
  10. 10.
    Kugler, A., Seseke, F., Thelen, P., Kallerhoff, M., Müller, G. A., Stuhler, G., et al. (1998) Autologous and allogeneic hybrid cell vaccine in patients with metastatic renal cell carcinoma. Brit. J. Urol. 82, 487–493.PubMedGoogle Scholar
  11. 11.
    Neil, G. A and Zimmermann, U. (1993) Electrofusion, in Methods in Enzymology (Moldave, K. and Grossman, L., eds.). Academic, New York, pp. 174–196.Google Scholar
  12. 12.
    Chesnut, R. W. and Grey, H. M. (1981) Studies on the capacity of B-cells to serve as antigen-presenting cells. J. Immunol. 126, 1075–1079.PubMedGoogle Scholar
  13. 13.
    Wen, Y. J., Ling, M., Bailey-Wood, R., and Lim, S. H. (1998) Idiotypic proteinpulsed adherent peripheral blood mononuclear cell derived dendritic cells primeimmune system in multiple myeloma. Clin. Cancer Res. 4, 957–962.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Uwe Trefzer
    • 1
  • Guido Weingart
    • 1
  • Wolfram Sterry
    • 2
  • Peter Walden
    • 2
  1. 1.Department of Dermatology, Medical Faculty CharitéHumboldt-University BerlinBerlinGermany
  2. 2.Department of Dermatology CharitéHumboldt University BerlinBerlinGermany

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