EFFECTIVENESS OF IMMUNOTHERAPY IN AGED LEUKEMIC MICE

We previously showed that immunotherapy using indomethacin combined wi th rIL-2 in vivo was very effective in stimulating natural killer (NK) cells and in increasing the life span of young adult mice bearing a t umor of hemopoietic origin. The aim of the present study was to test t he efficacy and universality, with respect to age, of this treatment i n tumor-bearing mice. DBA/2 mice (10-16 months old) were injected with 5 x 10(6) erythroleukemia cells and remained either: (i) untreated (c ontrol); (ii) treated with indomethacin (5 mu g/ml drinking water) for 9 days from tumor onset; (iii) treated with rIL-2 (24 x 10(3) U/injec tion) twice a day for the last 4 days of the 9-day tumor-bearing perio d, or (iv) treated with both indomethacin and rIL-2 concomitantly. Som e mice from each group (above) were killed after 9 days of tumor growt h, while the others were allowed to survive. Spleen and bone marrow ce lls were collected from the mice of each group and NK (ASGM-1+) cells were quantitated using an immunoperoxidase technique combined with lig ht microscopy. NK cell-mediated activity was assessed using a standard chromium release assay. The results show that although NK cell number s increase in the presence of the growing tumor, neither indomethacin alone, rIL-2 alone, nor the combination could further increase the num bers of these cells. Furthermore, indomethacin and/or rIL-2 could not induce NK cell-mediated activity in such mice. Moreover, tumor-bearing aged mice treated as above did not have a significantly longer life s pan than untreated (control) tumor-bearing mice. The present results i ndicate an age-dependent resistance to a form of immunotherapy already proven very effective in young adult mice. Furthermore, the results o f this and our previous studies suggest that immunotherapy, which may be highly effective in one age group, should not be presumed effective throughout life.