Improved therapeutic efficacy using vaccination with glioma lysate-pulsed dendritic cells combined with IP-10 in murine glioma

The purpose of the present study was to evaluate the therapeutic efficacy of glioma lysate-pulsed DCs in combination with plasmid DNA vector encoding the murine interferon-induced protein of 10 kDa (IP-10 or CXCL10) gene. Mouse models of brain glioma (GL261) were treated with combining glioma lysate-pulsed DCs with direct intraturnoral injection of a nonviral plasmid DNA vector encoding the murine IP-10 gene. The survival of mice bearing G1261 glioma was observed. Enzyme-linked immuno-spot assay was used to determine the frequency of brain-infiltrating lymphocytes (BILs) capable of responding to GL261. Cytolytic T lymphocyte (CTL) response was measured by cytotoxic assay. vessel density and tumor cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining. The results revealed that the combination therapy groups showed more significantly enhanced anti-tumor activity, attraction of lymphocytes into tumor tissues, apoptosis of tumor cells, and reduced neovascularization, cell proliferation, and developed a strong CTL response in these mice. In summary, the therapy of glioma lysate-pulsed DCs combined with the IP-10 gene has significant synergistic effect against glioma. (C) 2009 Elsevier Ltd. All rights reserved.