IMMUNOTHERAPY OF BALB C MICE BEARING EHRLICH ASCITES TUMOR WITH VITAMIN-D-BINDING PROTEIN-DERIVED MACROPHAGE ACTIVATING FACTOR/

Vitamin D-3-binding protein (DBP; human DBP is known as Gc protein) is the precursor of macrophage activating factor (MAF), Treatment of mou se DBP with immobilized beta-galactosidase or treatment of human Gc pr otein with immobilized beta-galactosidase and sialidase generated a re markably potent MAF, termed DBPMAF or GcMAF, respectively, The domain of Gc protein responsible for macrophage activation was cloned and enz ymatically converted to the cloned MAP, designated CdMAF. In Ehrlich a scites tumor-bearing mice, tumor-specific serum alpha-N-acetyl-galacto saminidase (NaGalase) activity increased linearly with time as the tra nsplanted tumor cells grew in the peritoneal cavity, Therapeutic effec ts of DBPMAF, GcMAF, and Cd;MAF on mice bearing Ehrlich ascites tumor were assessed by survival time, the total tumor cell count in the peri toneal cavity, and serum NaGalase activity, Mice that received a singl e administration of DBPMAF or GcMAF (100 pg/mouse) on the same day aft er transplantation of tumor (1 x 10(5) cells) showed a mean survival t ime of 35 +/- 4 days, whereas tumor-bearing controls had a mean surviv al time of 16 +/- 2 days, When mice received the second DBPMAF or GcMA F administration at day 4, they survived more than 50 days, Mice that received two DBPMAF administrations, at days 4 and 8 after transplanta tion of 1 x 10(5) tumor cells, survived up to 32 +/- 4 days, At day 4 posttransplantation, the total tumor cell count in the peritoneal cavi ty was approximately 5 x 10(5) cells, Mice that received two DBPMAF ad ministrations, at days 0 and 4 after transplantation of 5 x 10(5) tumo r cells, also survived up to 32 +/- 4 days, while control mice that re ceived the 5 x 10(5) ascites tumor cells only survived for 14 +/- 2 da ys, Four DBPMAF, GcMAF, or CdMAF administrations to mice transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals showed an extended survival of at least 90 days and an insignificantly low s erum NaGalase level between days 30 and 90.