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Clinical Trials |
Departments of Medicine [M. A. M.] and Surgery [Y. D., D. C., S. H., E. K-F., S. N., H. K. L.], Duke University Medical Center, Durham, North Carolina 27710; NIH, Bethesda, Maryland 20852 [J. S.]; and Schering-Plough Research Institute, Kenilworth, New Jersey 07033 [M-E. R.]
Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CEA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients‘ plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4. Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 107, 3 x 107, and 1 x 108 cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 106 DCs. There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies.
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M. D. Roth, B. J. Gitlitz, S. M. Kiertscher, A. N. Park, M. Mendenhall, N. Moldawer, and R. A. Figlin Granulocyte Macrophage Colony-stimulating Factor and Interleukin 4 Enhance the Number and Antigen-presenting Activity of Circulating CD14+ and CD83+ Cells in Cancer Patients Cancer Res., April 1, 2000; 60(7): 1934 - 1941. [Abstract] [Full Text]
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L. Fong, Y. Hou, A. Rivas, C. Benike, A. Yuen, G. A. Fisher, M. M. Davis, and E. G. Engleman Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy PNAS, July 17, 2001; 98(15): 8809 - 8814. [Abstract] [Full Text] [PDF]
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