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Preoperative Mobilization of Circulating Dendritic Cells by Flt3 Ligand Administration to Patients With Metastatic Colon Cancer

From the Departments of Medicine, Surgery, Immunology, and Pathology, Duke University Medical Center, Durham, NC, and Immunex, Corporation, Seattle, WA.

Address reprint requests to Michael A. Morse, MD, Duke University Medical Center, Box 2606, Durham, NC 27710.

PURPOSE: To evaluate preoperative dendritic cell (DC) mobilization and tumor infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer.

PATIENTS AND METHODS: Twelve patients with colon cancer metastatic to the liver or lung received Flt3L (20 µg/kg/d subcutaneously for 14 days for one to three cycles at monthly intervals) before attempted metastasectomy. The number and phenotype of DCs mobilized into peripheral-blood mononuclear cells (PBMCs) were evaluated by flow cytometry. After surgical resection, metastatic tumor tissue was evaluated for DC infiltration. In vivo immune responses to recall antigens were measured.

RESULTS: After Flt3L administration, on average, the total number of leukocytes in the peripheral blood increased from 5.9 ± 1.0 x 10³/mm³ to 11.2 ± 3.8 x 10³/mm³ (mean ± SD, P = .0001). The percentage of CD11c⁺CD14^- DCs in PBMCs increased from 2.4% ± 1.8% to 8.8% ± 4.7% (P = .004). Delayed-type hypersensitivity (DTH) responses to recall antigens (Candida, mumps, and tetanus) showed marginally significant increases in reactivity after Flt3L administration (P = .06, P = .03, and P = .08, respectively). An increase in the number of DCs was observed at the periphery of the tumors of patients who received Flt3L compared with those of patients who had not.

CONCLUSION: Flt3L is capable of mobilizing DCs into the peripheral blood of patients with metastatic colon cancer and may be associated with increases in DC infiltration in the peritumoral regions. Flt3L mobilization is associated with a trend toward increased DTH responses to recall antigens in vivo. The use of Flt3L to increase circulating DCs for cancer immunotherapy should be considered.

Portions of the data in this article were presented in abstract form: Morse M, Nair S, Fernandez-Casal M, et al: Flt3-ligand (FLT3L) mobilization of dendritic cells (DC) in patients with metastatic colon cancer. Blood 94:48a, 1999 (suppl 1, abstr 199).

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