Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model

Modalities that act through different mechanisms can often provide synergis tic antitumor activity for the treatment of refractory tumors when used in combination. Here we report a gene therapy approach in which the genes for the angiogenesis inhibitor, endostatin, and the marker protein and potent i mmunogen, green fluorescent protein (GFP), were delivered to murine neurobl astoma cells prior to inoculation of the tumor cells into syngeneic immunoc ompetent mice. Although the effect of either angiogenesis inhibition or imm unomodulation alone resulted in only a modest delay in tumor growth, when t hese approaches were used in combination, prevention of the formation of ap preciable tumors was effected in 15 of 24 (63%) mice. The combination of en dostatin and GFP expression elicited a strong immune response that was T ce ll-mediated and was reactive against both GFP and tumor cell line-specific antigens. This afforded treated mice protection against subsequent tumor ch allenge with unmodified tumor cells. These results suggest that antiangioge nic and immunotherapy strategies, when used in a gene therapy-mediated appr oach, can act synergistically in an effective multimodality anticancer appr oach.