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Progenipoietin (ProGP-4) is a chimeric molecule, exhibiting both Flt-3 and granulocyte-colony stimulating factor (G-CSF) receptor agonist activities. Subcutaneous administration of ProGP-4 to BALB/c mice at a dose of 40–100 μg/day for up to 12 consecutive days induces both CD11c+ dendritic cells (DCs) and CD11c−/CD11b+ granulocytes in spleen, blood and lymph nodes of treated animals. Peak numbers of all cell populations were observed on day 7 of treatment, with CD11c+ DCs representing approximately 8% of total splenocytes at that time. Approximately 40–50% of these CD11c+ cells were also able to endocytose and process the exogenous fluorescent antigen DQ-BSA. As a test of their therapeutic utility, freshly prepared CD11c+ DCs were pulsed with a defined tumor-associated peptide epitope (murine p53232–240) and injected as a vaccine into BALB/c mice bearing day 7 established CMS4 sarcomas. Similarly prepared DCs were injected again 1 week later. Based on our results, we conclude that (i) both peptide-pulsed CD11c+ DCs (harvested directly from ProGP-4 treated mice) and pulsed bone marrow-derived DCs effectively slow the growth of or mediate the regression (in 25 of 89 [28%] cases) of CMS4 tumors, and (ii) nonpulsed DCs mediated minimal or no therapeutic effect. These data support the ability of ProGP-4 to enhance the peripheral frequencies of DCs that exhibit therapeutic efficacy when applied as a vaccine to treat tumor-bearing animals. © 2002 Wiley-Liss, Inc. |
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