A phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen

Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstr ated to induce protective T cell-mediated immunity in tumor-bearing animals . We performed this study to test the safety, feasibility, and clinical res ponse of immunizations with in vitro-generated DCs, loaded with an HLA-A2-r estricted peptide fragment of the tumor antigen carcinoembryonic antigen (C EA), for the treatment of patients with advanced CPA-expressing malignancie s. Cell preparations enriched for autologous DCs were generated from the pa tients' plastic adherent peripheral blood mononuclear cells in serum-free m edia supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4, Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86(high), HLA-DRhigh, and CD14(low)). 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 10(7), 3 x 10(7), and 1 x 10(8 ) cells/dose. A subset of the patients in the last group also received intr adermal injections of 1 x 10(6) DCs, There were no toxicities directly refe rable to the treatments. One patient had a minor response, and one had stab le disease. Skin punch biopsy at DC injection sites demonstrated pleomorphi c infiltrates in the three patients evaluated. We conclude that it is feasi ble and safe to generate and administer large numbers of previously cryopre served DCs loaded with CAP-1 peptide to patients with advanced malignancies .