Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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).
Rosenberg, S.A. Immunotherapy of cancer using interleukin-2: Current status and future prospects. Immunol. Today 9, 58–62 (1988).
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).
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).
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).
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).
Mehta, D.A., Markowicz, S., and Engleman, E.G. Generation of antigen-specific CD8’ CTLs from naive precursors. J. Immunol. 153 996–1003(1994).
Romani, N., et al. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180, 83–93 (1994).
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).
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).
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).
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).
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).
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).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Alters, S.E., Gadea, J.R., Philip, R. (1997). Immunotherapy of Cancer. In: Ricciardi-Castagnoli, P. (eds) Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology, vol 417. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9966-8_85
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9966-8_85
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9968-2
Online ISBN: 978-1-4757-9966-8
eBook Packages: Springer Book Archive