1. ¹Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA
2. ²Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
3. ³MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
4. ⁴Canji Inc., San Diego, CA, USA
5. ⁵DNAX Research Institute, Palo Alto, CA, USA

Correspondence: Dr JC Solheim, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA. E-mail: jsolheim@unmc.edu

Received 2 August 2006; Accepted 4 November 2006; Published online 19 January 2007.

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.