Antitumor effects of recombinant human prolactin in human adenocarcinoma-bearing SCID mice with human NK cell xenograft.

To survey the immune regulatory function of recombinant human prolactin (rhPRL) and its potential application in adoptive immunotherapy, CB17-SCID mice were loaded with human colon adenocarcinoma HT-29 cells (5 x 10(5) cells/mouse, i.p.) 24 h before adoptive transfer with the purified human NK cells followed by rhPRL injection (10 mug/mouse, every other day for a total of 10 injections). Upon analysis, rhPRL did not exert any direct inhibitory effects on HT-29 cells but slightly improved the tumor cell growth both in vitro and in vivo. After SCID mice were reconstituted with human NK cells, rhPRL improved the antitumor effects of human NK cells in HT-29-bearing SCID mice, showing a prolonged survival from 70.4 to 112.1 days, and the increased survival rate from all died to 40% survival for more than 160 days. rhPRL improved the proliferation of human NK cells with or without PHA stimulation. rhPRL also directly enhanced the cytotoxicity of human NK cells against HT-29 tumor cells in 4-h coculture. The supernatant of rhPRL-stimulating NK cells inhibited the proliferation of HT-29 cells through, at least partly, the interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatant. Thus, rhPRL administration in HT-29 tumor-bearing SCID mice promotes the antitumor effects of adoptively transferred NK cells.