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 loca l sublethal radiation of tumors can synergistically enhance their sensitivi ty to immunotherapy with either systemic high-dose interleukin-2 (IL-2) or vaccination with autologous tumor cells expressing IL-2, interferon (IFN)-g amma and granulocyte-macrophage colony-stimulating factor (GM-CSF). Host an titumor 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 meta stasis model to investigate the efficacy of combined therapy with local tum or radiation and vaccination with IFN-alpha -secreting tumor cells (Renca/I FN-alpha), The in vitro and in vivo growth rates of Renca/IFN-alpha cells w ere significantly reduced relative to normal controls. Subcutaneous vaccina tion 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 co mbination of lung irradiation plus vaccination reduced the number of lung m etastases by 60%, and the net tumor volume by 95%. The reductions in tumor volume in both irradiated and non-irradiated lungs were comparable. These r esults indicate that host antitumor response to subcutaneous vaccination wi th Renca/IFN-alpha was systemic, and was significantly enhanced by radiatio n of tumor-bearing lungs. A regimen based on enhancement of IFN-alpha immun otherapy by local tumor radiation may be useful in the treatment of metasta tic renal cell carcinoma.