Infusion of Unpulsed Dendritic Cells Derived from Granulocyte/Macrophage Colony-Stimulating Factor-Mobilized Peripheral Blood CD34 + Cells and Monocytes in Patients with Advanced Carcinoma

Abstract

Dendritic cells are potent antigen-presenting cells that are reduced in number and function in cancer patients. The infusion of dendritic cells pulsed with tumor-associated antigens has demonstrated antitumor immunologic activity. The effects of dendritic cells derived from granulocyte/macrophage colony-stimulating factor (GM-CSF)-mobilized peripheral blood CD34⁺ cell and monocyte precursors when administered without antigen pulsing was examined. Patients with metastatic pancreatic and colorectal cancer received GM-CSF for 5 days. Blood was collected by a 250-ml phlebotomy. Dendritic cells were derived from CD34⁺ cells with culture in GM-CSF, tumor necrosis factor-α, and serum-free media or from monocytes with culture in GM-CSF, interleukin-4, and autologous serum. From 2.0 to 9.4 × 10⁶ dendritic cells were generated from CD34⁺ cells and from 71 × 10⁶ to 210 × 10⁶ dendritic cells were generated from monocytes. Dendritic cells generated from CD34⁺ cells expressed more CD1a than dendritic cells generated from monocytes; the ability to stimulate mixed lymphocyte reactions in vitro was not significantly different. Six patients received a single intravenous infusion of up to 5 × 10⁶ autologous CD34⁺ cell derived, and 6 patients, up to 50 × 10⁶ monocyte-derived dendritic cells. The infusion was well tolerated. Increases in skin test reactivity and peripheral blood proliferative responses to the recall antigen, candida, were observed after the infusion of dendritic cells of both derivations. Changes in skin test reactivity and peripheral blood proliferative responses to tumor-associated peptides, including Ras and Muc1, were not. Significant numbers of functionally competent dendritic cells can be generated from patients with advanced carcinoma after GM-CSF mobilization. The infusion of these dendritic cells has nonspecific immunomodulatory activity that may have clinical significance.