In vivo effects of recombinant interferon alpha A/D incorporated in gelatin microspheres on murine tumor cell growth.

Intraperitoneal (ip) injections of gelatin microspheres containing a very small amount of recombinant human interferon alpha A/D (A/D-IFN) (IFN-microspheres) plus free A/D-IFN improved the survival of mice bearing ascitic Meth A-R1 cells which we had isolated as IFN-resistant cells under in vitro conditions. The dose of free A/D-IFN in one injection was 10,000 IU, which was insufficient by itself for manifesting in vivo antitumor activity. In these mice, in vivo R1 cell growth was suppressed and macrophage recruitment was enhanced in comparison with mice receiving other control agents. Administration of IFN-microspheres alone was also effective but less than that of IFN-microspheres plus free A/D-IFN. Peritoneal macrophages obtained from normal or R1-bearing mice receiving ip injection of IFN-microspheres with or without free A/D-IFN were activated to inhibit the in vitro growth of R1 cells. The intratumoral injection of IFN-microspheres strongly inhibited the growth of solid R1 tumors. Intravenous injection of IFN-microspheres was effective in preventing the pulmonary metastasis of B16 melanoma cells. These results indicate that the IFN-microsphere is much more effective against tumors than free A/D-IFN.