Immunotherapy of Cancer

Generation of CEA Specific CTL Using CEA Peptide Pulsed Dendritic Cells
  • Susan E. Alters
  • Jose R. Gadea
  • Ramila Philip
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)


Antigen specific cytotoxic T lymphocytes (CTL) are being studied for their potential immunotherapeutic benefit in the treatment of cancer. Carcinoembryonic antigen (CEA) is an oncofetal protein best known for its overexpression in the majority of colorectal, gastric, pancreatic, non small cell lung, and breast carcinomas. We are using dendritic cells (DC) pulsed with the CEA CTL peptide epitope to generate CEA specific CTL. DC from HLA A2+ donors were isolated by culturing plastic adherent PBMC in GMCSF and 1L4 for 7 days. As expected these DC expressed the relevant cell surface molecules including HLA DR, CD58, CD80, and CD86. The DC were strippped of their endogenous peptides, pulsed with the A2 restricted CEA peptide, irradiated and used to stimulate autologous CD8+ T cells in the presence of 1L7. Using this approach we have been able to generate CEA specific CTL from the PBMC of breast and pancreatic carcinoma patients as well as normal donors. These CTL can lyse CEA peptide pulsed T2 targets as well as HLA A2+ tumor cells expressing the CEA antigen. This data is being used to support a phase I active immunotherapy clinical protocol using DC pulsed with CEA peptide to treat patients with metastatic malignancies expressing CEA.


Dendritic Cell Peptide Pulse Dendritic Cell Pulse Dendritic Cell Oncofetal Protein Pancreatic Carcinoma Patient 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rosenberg, S. A et. al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N. Engl. J. Med. 316, 889–897 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    Rosenberg, S.A. Immunotherapy of cancer using interleukin-2: Current status and future prospects. Immunol. Today 9, 58–62 (1988).Google Scholar
  3. 3.
    Rosenberg, S.A., et al. Experience with the use of high-dose interleukin-2 in the treatment of 652 patients with cancer. Ann. Surg. 210, 474–85 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson, J.A., Gruner, F., and Zimmermann, W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J. Clin. Lab. Anal. 5, 344–366 (1991).PubMedCrossRefGoogle Scholar
  5. 5.
    Tsang, K. Y., et al. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J. Natl. Canc. Ins. 87, 982990 (1995).Google Scholar
  6. 6.
    Inaba, K., Metly, P.J., Crowley, M.T., and Steinman, R.M. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med. 172, 631–640 (1990).PubMedCrossRefGoogle Scholar
  7. 7.
    Mehta, D.A., Markowicz, S., and Engleman, E.G. Generation of antigen-specific CD8’ CTLs from naive precursors. J. Immunol. 153 996–1003(1994).Google Scholar
  8. 8.
    Romani, N., et al. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180, 83–93 (1994).PubMedCrossRefGoogle Scholar
  9. 9.
    Mehta, D.A., Markowicz, S., and Engleman, E.G. Generation of antigen-specific CD4` T cell lines from naive precursors. Eur. J. Immunol. 25, 206–1211 (1995).Google Scholar
  10. 10.
    Mayordomo, J.1., et al. Bone marrow-derived dendritic cells pulsed with synthetic tumor peptides elicit protective and therapeutic antitumour immunity. Nature Med. 1(12), 1297–1302 (1995).Google Scholar
  11. 11.
    Celluzzi, C.M., Mayordomo, J.I., Storkus, W.J., Lotze, M.T., and Falo, L.D. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J. Exp. Med. 183, 283–287 (1996).PubMedCrossRefGoogle Scholar
  12. 12.
    Zitvogel, L., et. al. Therapy of murine tumors with tumor peptide-pulsed dendritic cells: Dependence on T cell, B7 costimulation, and T helper cell 1-associated cytokines. J. Exp. Med. 183, 87–97 (1996).PubMedCrossRefGoogle Scholar
  13. 13.
    Ossevoort, M.A., Feltamp, M.C.W., van Veen, K.J.H., Melief, C.J.M., and Kast, W.M. Dendritic cells as carriers for a cytotoxic T-lymphocyte epitope-based peptide vaccine in protection against a human papillomavirus type 16-induced tumor. J. Immunother. 18, 86–94 (1995).CrossRefGoogle Scholar
  14. 14.
    Porgador, A., and Gilboa, E. Bone-marrow-generated dendritic cells pulsed with a class 1-restricted peptide are potent inducers of cytotoxic T lymphocytes. J. Exp. Med. 182, 255–260 (1995).PubMedCrossRefGoogle Scholar
  15. 15.
    Bakker, A. B., et. al. Generation of antimelanoma cytotoxic T lymphocytes from healthy donors after presentation of melanoma-associated antigen-derived epitopes by dendritic cells in vitro. Cancer Res. 55, 5330–5334 (1995).Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Susan E. Alters
    • 1
  • Jose R. Gadea
    • 1
  • Ramila Philip
    • 1
  1. 1.RPR GenCellSanta ClaraUSA

Personalised recommendations