Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine

We have previously demonstrated in a murine lung metastasis model that local sublethal radiation of tumors can synergistically enhance their sensitivity to immunotherapy with either systemic high-dose interleukin-2 (IL-2) or vaccination with autologous tumor cells expressing IL-2, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF). Host antitumor activity was mediated in large part by natural killer cells, which can be activated by IFN-alpha. In the present study, we used this lung metastasis model to investigate the efficacy of combined therapy with local tumor radiation and vaccination with IFN-alpha-secreting tumor cells (Renca/IFN-alpha). The in vitro and in vivo growth rates of Renca/IFN-alpha cells were significantly reduced relative to normal controls. Subcutaneous vaccination with Renca/IFN-alpha or selective X-irradiation of the left lung (300 rad) reduced the number of lung tumors by 40% and 27%, respectively. The combination of lung irradiation plus vaccination reduced the number of lung metastases by 60%, and the net tumor volume by 95%. The reductions in tumor volume in both irradiated and non-irradiated lungs were comparable. These results indicate that host antitumor response to subcutaneous vaccination with Renca/IFN-alpha was systemic, and was significantly enhanced by radiation of tumor-bearing lungs. A regimen based on enhancement of IFN-alpha immunotherapy by local tumor radiation may be useful in the treatment of metastatic renal cell carcinoma.