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Cancer Gene Ther ; 14(4): 364-71, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17235356

ABSTRACT

Dendritic cell (DC) expansion is regulated by the hematopoietic growth factor fms-like tyrosine kinase 3 ligand (Flt3L). DCs are critical to the control of tumor growth and metastasis, and there is a positive correlation between intratumoral DC infiltration and clinical outcome. In this report, we first demonstrate that single intravenous (i.v.) injections of adenovirus (Adv)-Flt3L significantly increased splenic dendritic, B, T and natural killer (NK) cell numbers in both normal and mammary tumor-bearing mice. In contrast, the numbers of DCs and T cells infiltrating the tumors were not increased. Consistent with the minimal effect on immune cell infiltration, i.v. Adv-Flt3L injections had no therapeutic activity against orthotopic mammary tumors. In addition, we noted tumor and Adv-Flt3L expansion of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs), which may inhibit the therapeutic efficacy of Adv-Flt3L-expanded DCs.


Subject(s)
Genetic Therapy , Mammary Neoplasms, Animal/therapy , Membrane Proteins/genetics , Spleen/immunology , T-Lymphocytes/immunology , Adenoviridae/genetics , Animals , Dendritic Cells/immunology , Female , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Injections, Intravenous , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Inbred BALB C , Treatment Failure
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