Successful induction of clinically competent dendr

Authors: Yuji Ueda Tsuyoshi Itoh Nobuaki Fuji Sachio Harada Hiroshi Fujiki Keiji Shimizu Atsushi Shiozaki Arihiro Iwamoto Takeshi Shimizu Osam Mazda Takafumi Kimura Yoshiaki Sonoda Masafumi Taniwaki Hisakazu Yamagishi

Publish Date: 2006/07/08

Volume: 56, Issue: 3, Pages: 381-

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Abstract

Recent studies have suggested that dendritic cell DCbased immunotherapy is one promising approach for the treatment of cancer We previously studied the clinical toxicity feasibility and efficacy of cancer vaccine therapy with peptidepulsed DCs In that study we used granulocyte colonystimulating factor GCSFmobilized peripheral blood monocytes as a cell source of DCs However previous investigations have suggested that GCSFmobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin IL12 and tumor necrosis factor TNFα These T helper Th1type cytokines are thought to promote antitumor immune response In this study we assessed the functional abilities of DCs generated from GCSFmobilized monocytes obtained from 13 patients with CEApositive advanced solid cancers Peripheral blood mononuclear cells were obtained from leukapheresis products collected before and after systemic administration of GCSF subcutaneous administration of highdose 5–10 μg/kg human recombinant GCSF for five consecutive days In vitro cytokine production profiles after stimulation with lipopolysaccharide LPS were compared between monocytes with and without GCSF mobilization DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptidespecific T cell responses Administration of GCSF was found to efficiently mobilize peripheral blood monocytes Although GCSFmobilized monocytes G/Mo less effectively produced Th1type cytokines than control monocytes C/Mo DCs generated from G/Mo restored the same level of IL12 production as that seen in DCs generated from C/Mo T cell induction assay using recall antigen peptide and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated from C/Mo Our results suggest that GCSF mobilization can be used to collect monocytes as a cell source for the generation of DCs for cancer immunotherapy DCs generated in this fashion were pulsed with HLAA24restricted CEA epitope peptide and administered to patients safely immunological responses were induced in some patients

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