Immunotherapy of the SL2-5 murine lymphoma with natural killer cells and tamoxifen or toremifene.

It is well established that tamoxifen (TX) has a therapeutic effect on estrogen receptor positive tumors by inhibiting the binding of estradiol to its receptor. However, repeated clinical observations indicate that tamoxifen may also have beneficial effects on estrogen receptor negative tumors. In vitro cytotoxicity experiments were performed with the SL2-5 murine lymphoma using interleukin (IL)-2 activated syngeneic NK cells as effectors with or without TX or TO treatment. The effect of TX or TO (10 mg/kg/day/animal in feed) on the immunotherapy of SL2-5 lymphoma with syngeneic IL-2 activated NK cells was also investigated in syngeneic DBA/2 mice. Assays of SL2-5 cells for estrogen and progesterone receptors were also performed. Both TX and TO enhanced significantly the susceptibility of the SL2-5 lymphoma to lysis by IL-2 activated NK cells in vitro. When TX or TO treatment was combined with NK cell immunotherapy of this tumor, both drugs potentiated significantly tumor regression and cure rate when compared to groups receiving NK therapy alone. This tumor does not express classical receptors for estrogens or progesterone. These results indicate that combination treatment with the antiestrogens, TX and TO, acts synergistically with the immunotherapeutic effect of IL-2 activated NK cells in a syngeneic tumor host system.