Progenipoietin‐generated dendritic cells exhibit anti‐tumor efficacy in a therapeutic murine tumor model

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Abstract
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.
Funding Information
  • Pharmacia